Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limit...Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.展开更多
Objective This study aimed to develop and test a model for predicting dysthyroid optic neuropathy(DON)based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid(CSF)in the optic nerve she...Objective This study aimed to develop and test a model for predicting dysthyroid optic neuropathy(DON)based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid(CSF)in the optic nerve sheath.Methods This retrospective study included patients with thyroid-associated ophthalmopathy(TAO)without DON and patients with TAO accompanied by DON at our hospital.The imaging markers of the optic nerve and CSF in the optic nerve sheath were measured on the water-fat images of each patient and,together with clinical factors,were screened by Least absolute shrinkage and selection operator.Subsequently,we constructed a prediction model using multivariate logistic regression.The accuracy of the model was verified using receiver operating characteristic curve analysis.Results In total,80 orbits from 44 DON patients and 90 orbits from 45 TAO patients were included in our study.Two variables(optic nerve subarachnoid space and the volume of the CSF in the optic nerve sheath)were found to be independent predictive factors and were included in the prediction model.In the development cohort,the mean area under the curve(AUC)was 0.994,with a sensitivity of 0.944,specificity of 0.967,and accuracy of 0.901.Moreover,in the validation cohort,the AUC was 0.960,the sensitivity was 0.889,the specificity was 0.893,and the accuracy was 0.890.Conclusions A combined model was developed using imaging data of the optic nerve and CSF in the optic nerve sheath,serving as a noninvasive potential tool to predict DON.展开更多
AIM:To assess the repeatability,interocular correlation,and agreement of quantitative swept-source optical coherence tomography angiography(OCTA)optic nerve head(ONH)parameters in healthy subjects.METHODS:Thir ty-thre...AIM:To assess the repeatability,interocular correlation,and agreement of quantitative swept-source optical coherence tomography angiography(OCTA)optic nerve head(ONH)parameters in healthy subjects.METHODS:Thir ty-three healthy subjects were enrolled.The ONH of both eyes were imaged four times by a swept-source-OCTA using a 3 mm×3 mm scanning protocol.Images of the radial peripapillary capillary were analyzed by a customized Matlab program,and the vessel density,fractal dimension,and vessel diameter index were measured.The repeatability of the four scans was determined by the intraclass correlation coefficient(ICC).The most well-centered optic disc from the four repeated scans was then selected for the interocular correlation and agreement analysis using the Pearson correlation coefficient,ICC and Bland-Altman plots.RESULTS:All swept-source-OCTA ONH parameters exhibited certain repeatability,with ICC>0.760 and coefficient of variation(CoV)≤7.301%.The obvious interocular correlation was observed for papillary vessel density(ICC=0.857),vessel diameter index(ICC=0.857)and fractal dimension(ICC=0.906),while circumpapillary vessel density exhibited moderate interocular correlation(ICC=0.687).Bland-Altman plots revealed an agreement range of-5.26%to 6.21%for circumpapillary vessel density.CONCLUSION:OCTA ONH parameters demonstrate good repeatability in healthy subjects.The interocular correlations of papillary vessel density,fractal dimension and vessel diameter index are high,but the correlation for circumpapillary vessel density is moderate.展开更多
BACKGROUND:As advocated in advanced trauma life support and prehospital trauma life support protocols,cervical immobilization is applied until cervical spine injury is excluded.This study aimed to show the difference ...BACKGROUND:As advocated in advanced trauma life support and prehospital trauma life support protocols,cervical immobilization is applied until cervical spine injury is excluded.This study aimed to show the difference in optic nerve sheath diameter(ONSD)between patients with and without a cervical collar using computed tomography(CT).METHODS:This was a single-center,retrospective study examining trauma patients who presented to the emergency department between January 1,2021,and December 31,2021.The ONSD on brain CT of the trauma patients was measured and analyzed to determine whether there was a difference between the ONSD with and without the cervical collar.RESULTS:The study population consisted of 169 patients.On CT imaging of patients with(n=66)and without(n=103)cervical collars,the mean ONSD in the axial plane were 5.43±0.50 mm and 5.04±0.46 mm respectively for the right eye and 5.50±0.52 mm and 5.11±0.46 mm respectively for the left eye.The results revealed an association between the presence of a cervical collar and the mean ONSD,which was statistically significant(P<0.001)for both the right and left eyes.CONCLUSION:A cervical collar may be associated with increased ONSD.The effect of this increase in the ONSD on clinical outcomes needs to be investigated,and the actual need for cervical collar in the emergency department should be evaluated on a case-by-case basis.展开更多
Glaucoma is a common and complex neurodegenerative disease characterized by progressive loss of retinal ganglion cells(RGCs)and axons.Currently,there is no effective method to address the cause of RGCs degeneration.Ho...Glaucoma is a common and complex neurodegenerative disease characterized by progressive loss of retinal ganglion cells(RGCs)and axons.Currently,there is no effective method to address the cause of RGCs degeneration.However,studies on neuroprotective strategies for optic neuropathy have increased in recent years.Cell replacement and neuroprotection are major strategies for treating glaucoma and optic neuropathy.Regenerative medicine research into the repair of optic nerve damage using stem cells has Received considerable attention.Stem cells possess the potential for multidirectional differentiation abilities and are capable of producing RGCfriendly microenvironments through paracrine effects.This article reviews a thorough researches of recent advances and approaches in stem cell repair of optic nerve injury,raising the controversies and unresolved issues surrounding the future of stem cells.展开更多
BACKGROUND Neuromonitoring in medical intensive care units is challenging as most patients are unfit for invasive intracranial pressure(ICP)modalities or unstable to transport for imaging.Ultrasonography-based optic n...BACKGROUND Neuromonitoring in medical intensive care units is challenging as most patients are unfit for invasive intracranial pressure(ICP)modalities or unstable to transport for imaging.Ultrasonography-based optic nerve sheath diameter(ONSD)is an attractive option as it is reliable,repeatable and easily performed at the bedside.It has been sufficiently validated in traumatic brain injury(TBI)to be incorporated into the guidelines.However,currently the data for non-TBI patients is inconsistent for a scientific recommendation to be made.AIM To compile the existing evidence for understanding the scope of ONSD in measuring ICP in adult non-traumatic neuro-critical patients.METHODS PubMed,Google Scholar and research citation analysis databases were searched for studies in adult patients with non-traumatic causes of raised ICP.Studies from 2010 to 2024 in English languages were included.RESULTS We found 37 articles relevant to our search.The cutoff for ONSD in predicting ICP varied from 4.1 to 6.3 mm.Most of the articles used cerebrospinal fluid opening pressure followed by raised ICP on computed tomography/magnetic resonance imaging as the comparator parameter.ONSD was also found to be a reliable outcome measure in cases of acute ischaemic stroke,intracerebral bleeding and intracranial infection.However,ONSD is of doubtful utility in septic metabolic encephalopathy,dysnatremias and aneurysmal subarachnoid haemorrhage.CONCLUSION ONSD is a useful tool for the diagnosis of raised ICP in non-traumatic neuro-critically ill patients and may also have a role in the prognostication of a subset of patients.展开更多
Objective:A comprehensive meta-analysis based on the latest randomized controlled trials(RCTs)was conducted to investigate the effects of transcutaneous electrical nerve stimulation(TENS)on patients undergoing treatme...Objective:A comprehensive meta-analysis based on the latest randomized controlled trials(RCTs)was conducted to investigate the effects of transcutaneous electrical nerve stimulation(TENS)on patients undergoing treatment after inguinal hernia surgery.Methods:A detailed search of Embase,PubMed,Web of Science,and the Cochrane Library was performed for RCTs investigating the use of TENS during inguinal hernia surgery up to September 28,2021.The Cochrane tool was applied to assess the risk of bias in the included studies.Results:Seven eligible RCTs with a total of 379 cases were included.The meta-analysis showed a mean difference(MD)in VAS of-1.61[95%CI:-2.20-1.02,P<0.00001]at 2 hours post-operation,VAS MD=-1.33 at 4 hours post-operation[95%CI:-2.84-0.18,P=0.09],VAS MD=-2.36 at 8 hours post-operation[95%CI:-4.04-0.69,P=0.006],and VAS MD=-1.75 at 24 hours post-operation[95%CI:-2.64-0.85,P=0.0001].The cortisol level MD at 24 hours post-operation was-52.56[95%CI:-168.8-63.76,P=0.38].Conclusion:TENS significantly reduces postoperative pain following inguinal hernia surgery and promotes patient recovery.TENS is recommended for patients undergoing inguinal hernia surgery.However,further high-quality studies are needed to confirm additional effects.展开更多
AIM: To evaluate the effect of femtosecond laser-assisted lens surgery(FLALS;cataract surgery or refractive lens exchange) on the structure of the optic nerve head and the macula.METHODS: This prospective longitudinal...AIM: To evaluate the effect of femtosecond laser-assisted lens surgery(FLALS;cataract surgery or refractive lens exchange) on the structure of the optic nerve head and the macula.METHODS: This prospective longitudinal study included healthy eyes undergoing FLALS. Eyes with glaucoma or any other ocular disease that could alter optical coherence tomography results were excluded. Retinal nerve fiber layer(RNFL), Bruch’s membrane opening-minimum rim width(BMO-MRW) and macular thickness(MT) were measured preoperatively, 1 and 6 mo after surgery using spectral-domain optical coherence tomography(SD-OCT). Changes between preoperative and postoperative values were evaluated.RESULTS: A total of 87 eyes of 46 patients were included in this study. Preoperative RNFL, BMO-MRW and MT in microns(μm) were 100.77±10.39, 330.31±49.99 and 276.30±33.39, respectively. Postoperative RNFL, BMO-MRW and MT were 104.74±11.55, 348.32±54.05 and 279.83±22.65 1 mo after surgery and 102.93±11.17, 343.11±53.4 and 278.90±22.19 6 mo after surgery, respectively;which equals an increase of 3.93%, 5.45% and 1.27%,respectively, 1 mo after surgery, and 2.14%, 3.87% and 0.94% 6 mo after surgery. The differences between the preoperative and the postoperative RNFL and BMO-MRW values were statistically significant(P<0.001). Regarding MT values, there were not statistically significant differences(P=0.26).CONCLUSION: Our study suggests that FLALS does not have a negative impact on the structural status of the optic nerve head in healthy eyes, assessed by SD-OCT. There is a slight increase in the values of RNFL, BMO-MRW and MT 1 mo and 6 mo after surgery.展开更多
·AIM:To evaluate optic nerve head(ONH)vessel density(VD)changes after cataract surgery using optical coherence tomography angiography(OCTA).·METHODS:This was a prospective observational study.Thirty-four eye...·AIM:To evaluate optic nerve head(ONH)vessel density(VD)changes after cataract surgery using optical coherence tomography angiography(OCTA).·METHODS:This was a prospective observational study.Thirty-four eyes with mild/moderate cataracts were included.ONH scans were obtained before and 3mo after cataract surgery using OCTA.Radial peripapillary capillary(RPC)density,all VD,large VD and retinal nerve fiber layer thickness(RNFLT)in total disc,inside disc,and different peripapillary sectors were assessed and analyzed.Image quality score(QS),fundus photography grading and bestcorrected visual acuity(BCVA)were also collected,and correlation analyses were performed between VD change and these parameters.·RESULTS:Compared with baseline,both RPC and all VD increased in inside disc area 3mo postoperatively(from 47.5%±5.3%to 50.2%±3.7%,and from 57.87%±4.30%to 60.47%±3.10%,all P<0.001),but no differences were observed in peripapillary area.However,large VD increased from 5.63%±0.77%to 6.47%±0.72%in peripapillary ONH region(P<0.001).RPC decreased in inferior and superior peripapillary ONH parts(P=0.019,<0.001 respectively).There were obvious negative correlations between RPC change and large VD change in inside disc,superior-hemi,and inferior-hemi(r=-0.419,-0.370,and-0.439,P=0.017,0.044,and 0.015,respectively).No correlations were found between VD change and other parameters including QS change,fundus photography grading,postoperative BCVA,and postoperative peripapillary RNFLT.·CONCLUSION:RPC density and all VD in the inside disc ONH region increase 3mo after surgery in patients with mild to moderate cataract.No obvious VD changes are found in peripapillary area postoperatively.展开更多
Objective To evaluate the optic nerve impairment using MRI histogram texture analysis in the patients with optic neuritis.Methods The study included 60 patients with optic neuritis and 20 normal controls. The coronal ...Objective To evaluate the optic nerve impairment using MRI histogram texture analysis in the patients with optic neuritis.Methods The study included 60 patients with optic neuritis and 20 normal controls. The coronal T2 weighted imaging(T2 WI) with fat saturation and enhanced T1 weighted imaging(T1 WI) were performed to evaluate the optic nerve. MRI histogram texture features of the involved optic nerve were measured on the corresponding coronal T2 WI images. The normal optic nerve(NON) was measured in the posterior 1/3 parts of the optic nerve. Kruskal-Wallis one-way ANOVA was used to compare the difference of texture features and receiver operating characteristic(ROC) curve were performed to evaluate the diagnostic value of texture features for the optic nerve impairment among the affected optic nerve with enhancement(ONwEN), affected optic nerve without enhancement(ONwoEN), contralateral normal appearing optic nerve(NAON) and NON. Results The histogram texture Energy and Entropy presented significant differences for ONwEN vs. ONwoEN(both P = 0.000), ONwEN vs. NON(both P = 0.000) and NAON vs. NON(both P < 0.05). ROC analysis demonstrated that the area under the curve(AUC) of histogram texture Energy were 0.758, 0.795 and 0.701 for ONwEN vs. ONwoEN, ONwEN vs. NON and NAON vs. NON, AUC of Entropy were 0.758, 0.795 and 0.707 for ONwEN vs. ONwoEN, ONwEN vs. NON and NAON vs. NON.Conclusion The altered MRI histogram texture Energy and Entropy could be considered as a surrogate for MRI enhancement to evaluate the involved optic nerve and normal-appearing optic nerve in optic neuritis.展开更多
There is a certain failure rate in traditional glaucoma surgery because of the lack of depth information in microscope images.In this work,we present a digital microscope-integrated optical coherence tomography(MIOCT)...There is a certain failure rate in traditional glaucoma surgery because of the lack of depth information in microscope images.In this work,we present a digital microscope-integrated optical coherence tomography(MIOCT)system and several custom-made OCT-compatible instruments for glaucoma surgery.Sixteen ophthalmologists were asked to perform trabeculectomy and canaloplasty on live porcine eyes using the system and instruments.After surgery,a subjective feedback survey about the user experience was taken.The experiment results showed that our system can help surgeons easily locate important tissue structures during surgery.The custom-made instruments also solved the shadowing problem in OCT imaging.Surgeons preferred to use the system in their future practice.展开更多
Rho-associated kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase RhoA. The Rho/ROCK pathway is closely related to the pathogenesis of several central nervous syst...Rho-associated kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase RhoA. The Rho/ROCK pathway is closely related to the pathogenesis of several central nervous system (CNS) disorders, and involved in many aspects of neuronal functions including neurite outgrowth and retraction. In the adult CNS, the damaged neuron regeneration is very difficult due to the presence of myelin-associated axon growth inhibitors such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (Omgp), etc. The effects of these axon growth inhibitors are reversed by blocking the Rho/ROCK pathway 47 vitro, and the inhibition of Rho/ROCK pathway can promote axon regeneration and functional recovery in the injured CNS in viva In addition, the therapeutic effects of the Rho/ROCK inhibitors have also been demonstrated in some animal models and the Rho/ROCK pathway becomes an attractive target for the development of drugs for treating CNS disorders. In this review, we summarized on the effect of the Rho and the downstream factor ROCK in neural regeneration, and the potential therapeutic effect of Rho/ROCK inhibitors in the survival and axonal regeneration of retinal ganglion cell was also discussed.展开更多
Our previous studies revealed that etomidate, a non-barbiturate intravenous anesthetic agent, has protective effects on retinal ganglion cells within 7 days after optic nerve transection. Whether this process is relat...Our previous studies revealed that etomidate, a non-barbiturate intravenous anesthetic agent, has protective effects on retinal ganglion cells within 7 days after optic nerve transection. Whether this process is related to anti-oxidative stress is not clear. To reveal its mechanism, we established the optic nerve transection injury model by transecting 1 mm behind the left eyeball of adult male Sprague-Dawley rats. The rats received an intraperitoneal injection of etomidate(4 mg/kg) once per day for 7 days. The results showed that etomidate significantly enhanced the number of retinal ganglion cells retrogradely labeled with Fluorogold at 7 days after optic nerve transection. Etomidate also significantly reduced the levels of nitric oxide and malonaldehyde in the retina and increased the level of glutathione at 12 hours after optic nerve transection. Thus, etomidate can protect retinal ganglion cells after optic nerve transection in adult rats by activating an anti-oxidative stress response. The study was approved by the Animal Ethics Committee at Air Force Medical University, China(approval No. 20180305) on March 5, 2018.展开更多
AIM: To evaluate the value of quantitative diffusion tensor imaging (DTI) in assessing the axonal and myelin damage of the optic nerves and optic radiations in patients with chronic primary angle -closure glaucoma (PA...AIM: To evaluate the value of quantitative diffusion tensor imaging (DTI) in assessing the axonal and myelin damage of the optic nerves and optic radiations in patients with chronic primary angle -closure glaucoma (PACG) by using high -field magnetic resonance (MR) imaging (3T). METHODS: Twenty patients with bilateral chronic PACG and twenty age - and sex matched disease -free control subjects were enrolled. Conventional MRI and DTI were performed on all subjects using 3T MR scanner. Mean diffusivity (MD), fractional anisotropy (FA), axial diffusivities (AD) and radial diffusivities (RD) of each optic nerve and each optic radiation were measured by using post -processing software of DTI studio 2.3, and then compared between left eyes and right eyes and between patients group and control group. The pairedsample t- test were used. RESULTS: There was no abnormality in the shape and signal intensity of the optic nerves and optic radiations in patients group and control group on the conventional MRI. No significant differences were observed in the FA, MD, AD and RD between the right and left optic nerves and optic radiations within patients group and control group (P>0.05). The optic nerves and optic radiations of patients with chronic PACG, as compared with control subjects, had significantly higher MD, AD, RD and significantly lower FA (P<0.05). CONCLUSION: The diffusivity of optic nerves and optic radiations in chronic PACG group showed abnormal and diffusivity parameters could be used markers of axonal and myelin injury in glaucoma.展开更多
We present the results from a patient with relapsing optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board ap- proved clinical trial and has beco...We present the results from a patient with relapsing optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board ap- proved clinical trial and has become the largest ophthalmology stem cell study registered at the National Institutes of Health to date (www.clinicaltrials.gov Identifier NCT 01920867). SCOTS utilizes autologous bone marrow-derived stem cells (BMSCs) for treatment of retinal and optic nerve diseases. Pre-treatment and post-treatment comprehensive eye exams of a 54 year old female patient were performed both at the Florida Study Center, USA and at The Eye Center of Columbus, USA. As a consequence of a relapsing optic neuritis, the patient's previously normal visual acuity decreased to between 20/350 and 20/400 in the right eye and to 20/70 in the left eye. Significant visual field loss developed bilaterally. The patient underwent a right eye vitrectomy with injection of BMSCs into the optic nerve of the right eyeand retrobulbar, subtenon and in- travitreal injection of BMSCs in the left eye. At 15 months after SCOTS treatment, the patient's visual acuity had improved to 20/150 in the right eye and 20/20 in the left eye. Bilateral visual fields improved markedly. Both macular thickness and fast retinal nerve fiber layer thickness were maximally improved at 3 and 6 months after SCOTS treatment. The patient also reduced her mycophenylate dose from 1,500 mg per day to 500 mg per day and required no steroid pulse therapy during the 15-month follow up.展开更多
The lack of axonal regeneration is the major cause of vision loss after optic nerve injury in adult mammals. Activating the PI3K/AKT/mTOR signaling pathway has been shown to enhance the intrinsic growth capacity of ne...The lack of axonal regeneration is the major cause of vision loss after optic nerve injury in adult mammals. Activating the PI3K/AKT/mTOR signaling pathway has been shown to enhance the intrinsic growth capacity of neurons and to facilitate axonal regeneration in the central nervous system after injury. The deletion of the mTOR negative regulator phosphatase and tensin homolog (PTEN) enhances regeneration of adult corticospinal neurons and ganglion cells. In the present study, we used a tyrosine-mutated (Y444F) AAV2 vector to efficiently express a short hairpin RNA (shRNA) for silencing PTEN expression in retinal ganglion cells. We evaluated cell survival and axonal regeneration in a rat model of optic nerve axotomy. The rats received an intravitreal injection of wildtype AAV2 or Y444F mutant AAV2 (both carrying shRNA to PTEN) 4 weeks before optic nerve axotomy. Compared with the wildtype AAV2 vector, the Y444F mutant AAV2 vector enhanced retinal ganglia cell survival and stimulated axonal regeneration to a greater extent 6 weeks after axotomy. Moreover,post-axotomy injection of the Y444F AAV2 vector expressing the shRNA to PTEN rescued ~19% of retinal ganglion cells and induced axons to regenerate near to the optic chiasm. Taken together, our results demonstrate that PTEN knockdown with the Y444F AAV2 vector promotes retinal ganglion cell survival and stimulates long-distance axonal regeneration after optic nerve axotomy. Therefore, the Y444F AAV2 vector might be a promising gene therapy tool for treating optic nerve injury.展开更多
AIM: To evaluate the effect of long weightlessness on retina and optic nerve in suspension (TS) rats. -term tail METHODS: A stimulated weightlessness model was established by suspending rats tail. After 12wk, the...AIM: To evaluate the effect of long weightlessness on retina and optic nerve in suspension (TS) rats. -term tail METHODS: A stimulated weightlessness model was established by suspending rats tail. After 12wk, the ultrastructure and the number of optic nerve axons were observed by transmission electron microscope. The number of survival retinal ganglion cells (RGCs) was calculated by fluorescent gold retrograde labeling. Retina cells apoptosis was detected by TUNEL staining. The function of optic nerve and retina was evaluated by the visual evoked potential (VEP) and oscillatory potentials (Ops). RESULTS: The optic nerve axons were swollen and sparsely aligned, and the lamellar separation and myelin disintegration occurred after 12wk in TS rats. The density of optic nerve axons was 32.23±3.92 ( ys 37.43±4.13, P= 0.0145), the RGCs density was 1645 ±46 cells/mm^2 (vs 1867±54 cells/mm^2 F=0.0000), the incidence rate of retinal cells apoptosis was 5.38%±0.53% ( vs 4.75%±0.54%, P= 0.0238), the amplitude of VEP-P100 was 15.43±2.14 μV (vs 17.67±2.17 μV, P=0.0424), the latency of VEP-P100 was 69.05v5.34ms (vs 62.43±4.87ms P=0.0143) and the sum amplitude of Ops was 81.05±8.34 μV (Ys 91.67± 10.21 μV, P=0.0280) in TS group and the control group, respectively. CONCLUSION: Long-term weightlessness can induce the ultrastructural changes and functional depress of the optic nerve, as well as retinal cell damages in TS rats.展开更多
AIM:To evaluate whether optical coherence tomography angiography(OCTA) can detect altered vessel density(VD) at the optic nerve head(ONH) in glaucoma patients.Special attention is paid to the accuracy of the OC...AIM:To evaluate whether optical coherence tomography angiography(OCTA) can detect altered vessel density(VD) at the optic nerve head(ONH) in glaucoma patients.Special attention is paid to the accuracy of the OCTA technique for distinguishing healthy from glaucomatous eyes.METHODS:A total of 171 eyes were examined by the OCTA system Angio Vue^TM(Optovue):97 eyes diagnosed with glaucoma and 74 healthy control eyes.The papillary and peripapillary VD was measured.Furthermore,the VD was correlated with different structural and functional measurements.In order to test the accuracy of differentiation between eyes with and without glaucoma,we calculated the receiver operating characteristic curve(ROC) and the area under the curve(AUC).RESULTS:The papillary and peripapillary VD in glaucomatous eyes was significantly lower than in healthy eyes(P〈0.05).The VD of the nasal peripapillary sector was significantly lower than in the other sectors.The further the disease had progressed [measured by determining the thickness of the ganglion cell complex(GCC) and the retinal nerve fiber layer(RNFL)] the greater the VD reduction.The AUC discriminated well between glaucomatous and normal eyes(consensus classifier 94.2%).CONCLUSION:OCTA allows non-invasive quantification of the peripapillary and papillary VD,which is significantly reduced in glaucomatous eyes and accurately distinguishes between healthy and diseased eyes.OCTA expands the spectrum of procedures for detecting and monitoring glaucoma.展开更多
AIM: To investigate the activation of autophagy in rat retina after optic nerve crush(ONC) and evaluate its relationship with apoptosis of retinal ganglion cells(RGCs).METHODS: The ONC model was established. Western b...AIM: To investigate the activation of autophagy in rat retina after optic nerve crush(ONC) and evaluate its relationship with apoptosis of retinal ganglion cells(RGCs).METHODS: The ONC model was established. Western blots were performed to investigate expression of p62, LC3 and Beclin-1. Transmission electron microscopy was performed to discover the autophagosomes in the retina after ONC. Immunohistochemistry was used to confirm the distribution of LC3. TUNEL was performed to confirm the relationship between autophagy and RGC apoptosis. RESULTS: p62/Beclin-1 ratio was declined shortly after ONC until to day 7 after ONC and then restored to a normal level at day 21. There was an opposite change in the LC3-II/LC3 I ratio in the retina compared to the p62/Beclin-1 ratio. Increased autophagosomes were found after ONC using transmission electron microscopy, and most of the LC3-stained cells were colocalized with RGCs and Müller cells. More LC3-immunoreactive cells and apoptotic RGCs were found on day 7 following ONC. CONCLUSION: Possible activation of autophagy in RGCs after ONC;autophagy mainly occurred in RGCs and Müller cells, and the apoptosis of RGCs after ONC may be partly associated with autophagic activation.展开更多
In this report, we present the results of a single patient with optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board approved clinical trial and...In this report, we present the results of a single patient with optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board approved clinical trial and is the largest ophthalmology stem cell study registered at the National Institutes of Health to date- www.clinicaltrials.gov Identifier NCT 01920867. SCOTS utilizes autologous bone marrow-derived stem cells in the treatment of optic nerve and retinal diseases. Pre- and post-treatment comprehensive eye exams were independently performed at the Wilmer Eye Institute at the Johns Hopkins Hospital, USA. A 27 year old female patient had lost vision approximately 5 years prior to enrollment in SCOTS. Pre-treatment best-corrected visual acuity at the Wilmer Eye Institute was 20/800 Right Eye (OD) and 20/4,000 Left Eye (OS). Four months following treatment in SCOTS, the central visual acuity had improved to 20/100 OD and 20/40 OS.展开更多
基金supported by the National Natural Science Foundation of China,No.82271114the Natural Science Foundation of Zhejiang Province of China,No.LZ22H120001(both to ZLC).
文摘Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.
基金supported financially by grants from the National Natural Science Foundation of China(No.81771793).
文摘Objective This study aimed to develop and test a model for predicting dysthyroid optic neuropathy(DON)based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid(CSF)in the optic nerve sheath.Methods This retrospective study included patients with thyroid-associated ophthalmopathy(TAO)without DON and patients with TAO accompanied by DON at our hospital.The imaging markers of the optic nerve and CSF in the optic nerve sheath were measured on the water-fat images of each patient and,together with clinical factors,were screened by Least absolute shrinkage and selection operator.Subsequently,we constructed a prediction model using multivariate logistic regression.The accuracy of the model was verified using receiver operating characteristic curve analysis.Results In total,80 orbits from 44 DON patients and 90 orbits from 45 TAO patients were included in our study.Two variables(optic nerve subarachnoid space and the volume of the CSF in the optic nerve sheath)were found to be independent predictive factors and were included in the prediction model.In the development cohort,the mean area under the curve(AUC)was 0.994,with a sensitivity of 0.944,specificity of 0.967,and accuracy of 0.901.Moreover,in the validation cohort,the AUC was 0.960,the sensitivity was 0.889,the specificity was 0.893,and the accuracy was 0.890.Conclusions A combined model was developed using imaging data of the optic nerve and CSF in the optic nerve sheath,serving as a noninvasive potential tool to predict DON.
基金Natural Science Foundation of Guangdong Province(No.2018A0303130306)Shantou Science and Technology Program(No.190917085269835,No.200629165261641).
文摘AIM:To assess the repeatability,interocular correlation,and agreement of quantitative swept-source optical coherence tomography angiography(OCTA)optic nerve head(ONH)parameters in healthy subjects.METHODS:Thir ty-three healthy subjects were enrolled.The ONH of both eyes were imaged four times by a swept-source-OCTA using a 3 mm×3 mm scanning protocol.Images of the radial peripapillary capillary were analyzed by a customized Matlab program,and the vessel density,fractal dimension,and vessel diameter index were measured.The repeatability of the four scans was determined by the intraclass correlation coefficient(ICC).The most well-centered optic disc from the four repeated scans was then selected for the interocular correlation and agreement analysis using the Pearson correlation coefficient,ICC and Bland-Altman plots.RESULTS:All swept-source-OCTA ONH parameters exhibited certain repeatability,with ICC>0.760 and coefficient of variation(CoV)≤7.301%.The obvious interocular correlation was observed for papillary vessel density(ICC=0.857),vessel diameter index(ICC=0.857)and fractal dimension(ICC=0.906),while circumpapillary vessel density exhibited moderate interocular correlation(ICC=0.687).Bland-Altman plots revealed an agreement range of-5.26%to 6.21%for circumpapillary vessel density.CONCLUSION:OCTA ONH parameters demonstrate good repeatability in healthy subjects.The interocular correlations of papillary vessel density,fractal dimension and vessel diameter index are high,but the correlation for circumpapillary vessel density is moderate.
文摘BACKGROUND:As advocated in advanced trauma life support and prehospital trauma life support protocols,cervical immobilization is applied until cervical spine injury is excluded.This study aimed to show the difference in optic nerve sheath diameter(ONSD)between patients with and without a cervical collar using computed tomography(CT).METHODS:This was a single-center,retrospective study examining trauma patients who presented to the emergency department between January 1,2021,and December 31,2021.The ONSD on brain CT of the trauma patients was measured and analyzed to determine whether there was a difference between the ONSD with and without the cervical collar.RESULTS:The study population consisted of 169 patients.On CT imaging of patients with(n=66)and without(n=103)cervical collars,the mean ONSD in the axial plane were 5.43±0.50 mm and 5.04±0.46 mm respectively for the right eye and 5.50±0.52 mm and 5.11±0.46 mm respectively for the left eye.The results revealed an association between the presence of a cervical collar and the mean ONSD,which was statistically significant(P<0.001)for both the right and left eyes.CONCLUSION:A cervical collar may be associated with increased ONSD.The effect of this increase in the ONSD on clinical outcomes needs to be investigated,and the actual need for cervical collar in the emergency department should be evaluated on a case-by-case basis.
基金Supported by Science&Technology Department of Sichuan Province(No.2021YFS0214).
文摘Glaucoma is a common and complex neurodegenerative disease characterized by progressive loss of retinal ganglion cells(RGCs)and axons.Currently,there is no effective method to address the cause of RGCs degeneration.However,studies on neuroprotective strategies for optic neuropathy have increased in recent years.Cell replacement and neuroprotection are major strategies for treating glaucoma and optic neuropathy.Regenerative medicine research into the repair of optic nerve damage using stem cells has Received considerable attention.Stem cells possess the potential for multidirectional differentiation abilities and are capable of producing RGCfriendly microenvironments through paracrine effects.This article reviews a thorough researches of recent advances and approaches in stem cell repair of optic nerve injury,raising the controversies and unresolved issues surrounding the future of stem cells.
文摘BACKGROUND Neuromonitoring in medical intensive care units is challenging as most patients are unfit for invasive intracranial pressure(ICP)modalities or unstable to transport for imaging.Ultrasonography-based optic nerve sheath diameter(ONSD)is an attractive option as it is reliable,repeatable and easily performed at the bedside.It has been sufficiently validated in traumatic brain injury(TBI)to be incorporated into the guidelines.However,currently the data for non-TBI patients is inconsistent for a scientific recommendation to be made.AIM To compile the existing evidence for understanding the scope of ONSD in measuring ICP in adult non-traumatic neuro-critical patients.METHODS PubMed,Google Scholar and research citation analysis databases were searched for studies in adult patients with non-traumatic causes of raised ICP.Studies from 2010 to 2024 in English languages were included.RESULTS We found 37 articles relevant to our search.The cutoff for ONSD in predicting ICP varied from 4.1 to 6.3 mm.Most of the articles used cerebrospinal fluid opening pressure followed by raised ICP on computed tomography/magnetic resonance imaging as the comparator parameter.ONSD was also found to be a reliable outcome measure in cases of acute ischaemic stroke,intracerebral bleeding and intracranial infection.However,ONSD is of doubtful utility in septic metabolic encephalopathy,dysnatremias and aneurysmal subarachnoid haemorrhage.CONCLUSION ONSD is a useful tool for the diagnosis of raised ICP in non-traumatic neuro-critically ill patients and may also have a role in the prognostication of a subset of patients.
文摘Objective:A comprehensive meta-analysis based on the latest randomized controlled trials(RCTs)was conducted to investigate the effects of transcutaneous electrical nerve stimulation(TENS)on patients undergoing treatment after inguinal hernia surgery.Methods:A detailed search of Embase,PubMed,Web of Science,and the Cochrane Library was performed for RCTs investigating the use of TENS during inguinal hernia surgery up to September 28,2021.The Cochrane tool was applied to assess the risk of bias in the included studies.Results:Seven eligible RCTs with a total of 379 cases were included.The meta-analysis showed a mean difference(MD)in VAS of-1.61[95%CI:-2.20-1.02,P<0.00001]at 2 hours post-operation,VAS MD=-1.33 at 4 hours post-operation[95%CI:-2.84-0.18,P=0.09],VAS MD=-2.36 at 8 hours post-operation[95%CI:-4.04-0.69,P=0.006],and VAS MD=-1.75 at 24 hours post-operation[95%CI:-2.64-0.85,P=0.0001].The cortisol level MD at 24 hours post-operation was-52.56[95%CI:-168.8-63.76,P=0.38].Conclusion:TENS significantly reduces postoperative pain following inguinal hernia surgery and promotes patient recovery.TENS is recommended for patients undergoing inguinal hernia surgery.However,further high-quality studies are needed to confirm additional effects.
文摘AIM: To evaluate the effect of femtosecond laser-assisted lens surgery(FLALS;cataract surgery or refractive lens exchange) on the structure of the optic nerve head and the macula.METHODS: This prospective longitudinal study included healthy eyes undergoing FLALS. Eyes with glaucoma or any other ocular disease that could alter optical coherence tomography results were excluded. Retinal nerve fiber layer(RNFL), Bruch’s membrane opening-minimum rim width(BMO-MRW) and macular thickness(MT) were measured preoperatively, 1 and 6 mo after surgery using spectral-domain optical coherence tomography(SD-OCT). Changes between preoperative and postoperative values were evaluated.RESULTS: A total of 87 eyes of 46 patients were included in this study. Preoperative RNFL, BMO-MRW and MT in microns(μm) were 100.77±10.39, 330.31±49.99 and 276.30±33.39, respectively. Postoperative RNFL, BMO-MRW and MT were 104.74±11.55, 348.32±54.05 and 279.83±22.65 1 mo after surgery and 102.93±11.17, 343.11±53.4 and 278.90±22.19 6 mo after surgery, respectively;which equals an increase of 3.93%, 5.45% and 1.27%,respectively, 1 mo after surgery, and 2.14%, 3.87% and 0.94% 6 mo after surgery. The differences between the preoperative and the postoperative RNFL and BMO-MRW values were statistically significant(P<0.001). Regarding MT values, there were not statistically significant differences(P=0.26).CONCLUSION: Our study suggests that FLALS does not have a negative impact on the structural status of the optic nerve head in healthy eyes, assessed by SD-OCT. There is a slight increase in the values of RNFL, BMO-MRW and MT 1 mo and 6 mo after surgery.
基金Supported by Natural Science Foundation of Zhejiang Province (No.LQ19H120001)。
文摘·AIM:To evaluate optic nerve head(ONH)vessel density(VD)changes after cataract surgery using optical coherence tomography angiography(OCTA).·METHODS:This was a prospective observational study.Thirty-four eyes with mild/moderate cataracts were included.ONH scans were obtained before and 3mo after cataract surgery using OCTA.Radial peripapillary capillary(RPC)density,all VD,large VD and retinal nerve fiber layer thickness(RNFLT)in total disc,inside disc,and different peripapillary sectors were assessed and analyzed.Image quality score(QS),fundus photography grading and bestcorrected visual acuity(BCVA)were also collected,and correlation analyses were performed between VD change and these parameters.·RESULTS:Compared with baseline,both RPC and all VD increased in inside disc area 3mo postoperatively(from 47.5%±5.3%to 50.2%±3.7%,and from 57.87%±4.30%to 60.47%±3.10%,all P<0.001),but no differences were observed in peripapillary area.However,large VD increased from 5.63%±0.77%to 6.47%±0.72%in peripapillary ONH region(P<0.001).RPC decreased in inferior and superior peripapillary ONH parts(P=0.019,<0.001 respectively).There were obvious negative correlations between RPC change and large VD change in inside disc,superior-hemi,and inferior-hemi(r=-0.419,-0.370,and-0.439,P=0.017,0.044,and 0.015,respectively).No correlations were found between VD change and other parameters including QS change,fundus photography grading,postoperative BCVA,and postoperative peripapillary RNFLT.·CONCLUSION:RPC density and all VD in the inside disc ONH region increase 3mo after surgery in patients with mild to moderate cataract.No obvious VD changes are found in peripapillary area postoperatively.
文摘Objective To evaluate the optic nerve impairment using MRI histogram texture analysis in the patients with optic neuritis.Methods The study included 60 patients with optic neuritis and 20 normal controls. The coronal T2 weighted imaging(T2 WI) with fat saturation and enhanced T1 weighted imaging(T1 WI) were performed to evaluate the optic nerve. MRI histogram texture features of the involved optic nerve were measured on the corresponding coronal T2 WI images. The normal optic nerve(NON) was measured in the posterior 1/3 parts of the optic nerve. Kruskal-Wallis one-way ANOVA was used to compare the difference of texture features and receiver operating characteristic(ROC) curve were performed to evaluate the diagnostic value of texture features for the optic nerve impairment among the affected optic nerve with enhancement(ONwEN), affected optic nerve without enhancement(ONwoEN), contralateral normal appearing optic nerve(NAON) and NON. Results The histogram texture Energy and Entropy presented significant differences for ONwEN vs. ONwoEN(both P = 0.000), ONwEN vs. NON(both P = 0.000) and NAON vs. NON(both P < 0.05). ROC analysis demonstrated that the area under the curve(AUC) of histogram texture Energy were 0.758, 0.795 and 0.701 for ONwEN vs. ONwoEN, ONwEN vs. NON and NAON vs. NON, AUC of Entropy were 0.758, 0.795 and 0.707 for ONwEN vs. ONwoEN, ONwEN vs. NON and NAON vs. NON.Conclusion The altered MRI histogram texture Energy and Entropy could be considered as a surrogate for MRI enhancement to evaluate the involved optic nerve and normal-appearing optic nerve in optic neuritis.
基金support of the foundations:National Key R&D Program of China,Grant Nos.2022YFC2404201CAS Project for Young Scientists in Basic Research,Grant Nos.YSBR-067+2 种基金The Gusu Innovation and Entrepreneurship Leading Talents in Suzhou City,Grant Nos.ZXL2021425Jiangsu Science and Technology Plan Program,Grant Nos.BK20220263National Key R&D Program of China,Grant Nos.2021YFF0700503.
文摘There is a certain failure rate in traditional glaucoma surgery because of the lack of depth information in microscope images.In this work,we present a digital microscope-integrated optical coherence tomography(MIOCT)system and several custom-made OCT-compatible instruments for glaucoma surgery.Sixteen ophthalmologists were asked to perform trabeculectomy and canaloplasty on live porcine eyes using the system and instruments.After surgery,a subjective feedback survey about the user experience was taken.The experiment results showed that our system can help surgeons easily locate important tissue structures during surgery.The custom-made instruments also solved the shadowing problem in OCT imaging.Surgeons preferred to use the system in their future practice.
基金Supported by National Nature Science Foundation of China (No.81070728)Shanghai "Science and Technology Innovation Action Plan" Basic Research Key Project,China (No.11JC1407700 and 11 JC1407701)+1 种基金Shanghai Nature Science Foundation, China (No.08ZR1413900)Shanghai Leading Academic Discipline Project, China(No.S30205)
文摘Rho-associated kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase RhoA. The Rho/ROCK pathway is closely related to the pathogenesis of several central nervous system (CNS) disorders, and involved in many aspects of neuronal functions including neurite outgrowth and retraction. In the adult CNS, the damaged neuron regeneration is very difficult due to the presence of myelin-associated axon growth inhibitors such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (Omgp), etc. The effects of these axon growth inhibitors are reversed by blocking the Rho/ROCK pathway 47 vitro, and the inhibition of Rho/ROCK pathway can promote axon regeneration and functional recovery in the injured CNS in viva In addition, the therapeutic effects of the Rho/ROCK inhibitors have also been demonstrated in some animal models and the Rho/ROCK pathway becomes an attractive target for the development of drugs for treating CNS disorders. In this review, we summarized on the effect of the Rho and the downstream factor ROCK in neural regeneration, and the potential therapeutic effect of Rho/ROCK inhibitors in the survival and axonal regeneration of retinal ganglion cell was also discussed.
基金supported by the National Natural Science Foundation of China,No.81670846(to MMW)and 81470631(to SWY)the Natural Science Foundation of Shaanxi Province of China,No.2016SF-171(to MMW)the National Basic Research Program of China,No.2014CB542202(to SWY)
文摘Our previous studies revealed that etomidate, a non-barbiturate intravenous anesthetic agent, has protective effects on retinal ganglion cells within 7 days after optic nerve transection. Whether this process is related to anti-oxidative stress is not clear. To reveal its mechanism, we established the optic nerve transection injury model by transecting 1 mm behind the left eyeball of adult male Sprague-Dawley rats. The rats received an intraperitoneal injection of etomidate(4 mg/kg) once per day for 7 days. The results showed that etomidate significantly enhanced the number of retinal ganglion cells retrogradely labeled with Fluorogold at 7 days after optic nerve transection. Etomidate also significantly reduced the levels of nitric oxide and malonaldehyde in the retina and increased the level of glutathione at 12 hours after optic nerve transection. Thus, etomidate can protect retinal ganglion cells after optic nerve transection in adult rats by activating an anti-oxidative stress response. The study was approved by the Animal Ethics Committee at Air Force Medical University, China(approval No. 20180305) on March 5, 2018.
文摘AIM: To evaluate the value of quantitative diffusion tensor imaging (DTI) in assessing the axonal and myelin damage of the optic nerves and optic radiations in patients with chronic primary angle -closure glaucoma (PACG) by using high -field magnetic resonance (MR) imaging (3T). METHODS: Twenty patients with bilateral chronic PACG and twenty age - and sex matched disease -free control subjects were enrolled. Conventional MRI and DTI were performed on all subjects using 3T MR scanner. Mean diffusivity (MD), fractional anisotropy (FA), axial diffusivities (AD) and radial diffusivities (RD) of each optic nerve and each optic radiation were measured by using post -processing software of DTI studio 2.3, and then compared between left eyes and right eyes and between patients group and control group. The pairedsample t- test were used. RESULTS: There was no abnormality in the shape and signal intensity of the optic nerves and optic radiations in patients group and control group on the conventional MRI. No significant differences were observed in the FA, MD, AD and RD between the right and left optic nerves and optic radiations within patients group and control group (P>0.05). The optic nerves and optic radiations of patients with chronic PACG, as compared with control subjects, had significantly higher MD, AD, RD and significantly lower FA (P<0.05). CONCLUSION: The diffusivity of optic nerves and optic radiations in chronic PACG group showed abnormal and diffusivity parameters could be used markers of axonal and myelin injury in glaucoma.
文摘We present the results from a patient with relapsing optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board ap- proved clinical trial and has become the largest ophthalmology stem cell study registered at the National Institutes of Health to date (www.clinicaltrials.gov Identifier NCT 01920867). SCOTS utilizes autologous bone marrow-derived stem cells (BMSCs) for treatment of retinal and optic nerve diseases. Pre-treatment and post-treatment comprehensive eye exams of a 54 year old female patient were performed both at the Florida Study Center, USA and at The Eye Center of Columbus, USA. As a consequence of a relapsing optic neuritis, the patient's previously normal visual acuity decreased to between 20/350 and 20/400 in the right eye and to 20/70 in the left eye. Significant visual field loss developed bilaterally. The patient underwent a right eye vitrectomy with injection of BMSCs into the optic nerve of the right eyeand retrobulbar, subtenon and in- travitreal injection of BMSCs in the left eye. At 15 months after SCOTS treatment, the patient's visual acuity had improved to 20/150 in the right eye and 20/20 in the left eye. Bilateral visual fields improved markedly. Both macular thickness and fast retinal nerve fiber layer thickness were maximally improved at 3 and 6 months after SCOTS treatment. The patient also reduced her mycophenylate dose from 1,500 mg per day to 500 mg per day and required no steroid pulse therapy during the 15-month follow up.
基金supported by the Research Foundation of Jiangsu Provincial Commission of Health and Family Planning of China,No.H201653the Research Foundation of Changshu Science and Technology Bureau of China,No.CS201616
文摘The lack of axonal regeneration is the major cause of vision loss after optic nerve injury in adult mammals. Activating the PI3K/AKT/mTOR signaling pathway has been shown to enhance the intrinsic growth capacity of neurons and to facilitate axonal regeneration in the central nervous system after injury. The deletion of the mTOR negative regulator phosphatase and tensin homolog (PTEN) enhances regeneration of adult corticospinal neurons and ganglion cells. In the present study, we used a tyrosine-mutated (Y444F) AAV2 vector to efficiently express a short hairpin RNA (shRNA) for silencing PTEN expression in retinal ganglion cells. We evaluated cell survival and axonal regeneration in a rat model of optic nerve axotomy. The rats received an intravitreal injection of wildtype AAV2 or Y444F mutant AAV2 (both carrying shRNA to PTEN) 4 weeks before optic nerve axotomy. Compared with the wildtype AAV2 vector, the Y444F mutant AAV2 vector enhanced retinal ganglia cell survival and stimulated axonal regeneration to a greater extent 6 weeks after axotomy. Moreover,post-axotomy injection of the Y444F AAV2 vector expressing the shRNA to PTEN rescued ~19% of retinal ganglion cells and induced axons to regenerate near to the optic chiasm. Taken together, our results demonstrate that PTEN knockdown with the Y444F AAV2 vector promotes retinal ganglion cell survival and stimulates long-distance axonal regeneration after optic nerve axotomy. Therefore, the Y444F AAV2 vector might be a promising gene therapy tool for treating optic nerve injury.
基金Supported by the National Natural Scientific Foundation of China (No. 81271016)
文摘AIM: To evaluate the effect of long weightlessness on retina and optic nerve in suspension (TS) rats. -term tail METHODS: A stimulated weightlessness model was established by suspending rats tail. After 12wk, the ultrastructure and the number of optic nerve axons were observed by transmission electron microscope. The number of survival retinal ganglion cells (RGCs) was calculated by fluorescent gold retrograde labeling. Retina cells apoptosis was detected by TUNEL staining. The function of optic nerve and retina was evaluated by the visual evoked potential (VEP) and oscillatory potentials (Ops). RESULTS: The optic nerve axons were swollen and sparsely aligned, and the lamellar separation and myelin disintegration occurred after 12wk in TS rats. The density of optic nerve axons was 32.23±3.92 ( ys 37.43±4.13, P= 0.0145), the RGCs density was 1645 ±46 cells/mm^2 (vs 1867±54 cells/mm^2 F=0.0000), the incidence rate of retinal cells apoptosis was 5.38%±0.53% ( vs 4.75%±0.54%, P= 0.0238), the amplitude of VEP-P100 was 15.43±2.14 μV (vs 17.67±2.17 μV, P=0.0424), the latency of VEP-P100 was 69.05v5.34ms (vs 62.43±4.87ms P=0.0143) and the sum amplitude of Ops was 81.05±8.34 μV (Ys 91.67± 10.21 μV, P=0.0280) in TS group and the control group, respectively. CONCLUSION: Long-term weightlessness can induce the ultrastructural changes and functional depress of the optic nerve, as well as retinal cell damages in TS rats.
文摘AIM:To evaluate whether optical coherence tomography angiography(OCTA) can detect altered vessel density(VD) at the optic nerve head(ONH) in glaucoma patients.Special attention is paid to the accuracy of the OCTA technique for distinguishing healthy from glaucomatous eyes.METHODS:A total of 171 eyes were examined by the OCTA system Angio Vue^TM(Optovue):97 eyes diagnosed with glaucoma and 74 healthy control eyes.The papillary and peripapillary VD was measured.Furthermore,the VD was correlated with different structural and functional measurements.In order to test the accuracy of differentiation between eyes with and without glaucoma,we calculated the receiver operating characteristic curve(ROC) and the area under the curve(AUC).RESULTS:The papillary and peripapillary VD in glaucomatous eyes was significantly lower than in healthy eyes(P〈0.05).The VD of the nasal peripapillary sector was significantly lower than in the other sectors.The further the disease had progressed [measured by determining the thickness of the ganglion cell complex(GCC) and the retinal nerve fiber layer(RNFL)] the greater the VD reduction.The AUC discriminated well between glaucomatous and normal eyes(consensus classifier 94.2%).CONCLUSION:OCTA allows non-invasive quantification of the peripapillary and papillary VD,which is significantly reduced in glaucomatous eyes and accurately distinguishes between healthy and diseased eyes.OCTA expands the spectrum of procedures for detecting and monitoring glaucoma.
基金Supported by Science and Technology Project of Nantong,China(No.MS22015002)
文摘AIM: To investigate the activation of autophagy in rat retina after optic nerve crush(ONC) and evaluate its relationship with apoptosis of retinal ganglion cells(RGCs).METHODS: The ONC model was established. Western blots were performed to investigate expression of p62, LC3 and Beclin-1. Transmission electron microscopy was performed to discover the autophagosomes in the retina after ONC. Immunohistochemistry was used to confirm the distribution of LC3. TUNEL was performed to confirm the relationship between autophagy and RGC apoptosis. RESULTS: p62/Beclin-1 ratio was declined shortly after ONC until to day 7 after ONC and then restored to a normal level at day 21. There was an opposite change in the LC3-II/LC3 I ratio in the retina compared to the p62/Beclin-1 ratio. Increased autophagosomes were found after ONC using transmission electron microscopy, and most of the LC3-stained cells were colocalized with RGCs and Müller cells. More LC3-immunoreactive cells and apoptotic RGCs were found on day 7 following ONC. CONCLUSION: Possible activation of autophagy in RGCs after ONC;autophagy mainly occurred in RGCs and Müller cells, and the apoptosis of RGCs after ONC may be partly associated with autophagic activation.
文摘In this report, we present the results of a single patient with optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board approved clinical trial and is the largest ophthalmology stem cell study registered at the National Institutes of Health to date- www.clinicaltrials.gov Identifier NCT 01920867. SCOTS utilizes autologous bone marrow-derived stem cells in the treatment of optic nerve and retinal diseases. Pre- and post-treatment comprehensive eye exams were independently performed at the Wilmer Eye Institute at the Johns Hopkins Hospital, USA. A 27 year old female patient had lost vision approximately 5 years prior to enrollment in SCOTS. Pre-treatment best-corrected visual acuity at the Wilmer Eye Institute was 20/800 Right Eye (OD) and 20/4,000 Left Eye (OS). Four months following treatment in SCOTS, the central visual acuity had improved to 20/100 OD and 20/40 OS.