Meningioma of the Optical Nerves in a Case at the Hospitalier Center of Saint Denis in Ile de France

Summary: Optic nerve tumors are rare tumors, representing 3% - 5% of intracranial tumors developing mainly along the optic nerve and/or the chiasm. Optic nerve meningiomas are histologically benign tumors whose severity is linked to diagnostic and especially therapeutic difficulties. The Optic nerve meningioma is the second leading cause of optic nerve tumor after glioma. Observation: We report the case of a 49-year-old woman from South Asia, who consults an ophthalmology department for progressive visual loss in her right eye for about a year with her glasses and would like to renew her optical correction. Having no particular medical history apart from left unilateral blindness is known for approximately 15 years. Magnetic Resonance Imaging (IRM) cerebral found a tissue mass with a clear outline and polylobules on the left temporo-peduncular. Through this case, we describe the circumstances of discovery of the disease, the clinical characteristics, as well as our diagnostic approach. Conclusion: In the majority of cases, these are benign tumours, the circumstances of which are discovered in multiple ways. A mostly unilateral and non-improvable loss of visual acuity must attract our attention. Renewing glasses may be the reason for discovering the disease. Today Magnetic Resonance Imaging (IRM) remains an important and capital examination for the diagnosis and monitoring of this pathology.

Repeatability,interocular correlation and agreement of optic nerve head vessel density in healthy eyes:a sweptsource optical coherence tomographic angiography study

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.

Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

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.

The optic nerve head perfusion and its correlation with the macular blood perfusion in unilateral idiopathic macular hole： an optical coherence tomography angiography study

AIM： To compare the optic nerve head （ONH） perfusion in both eyes of unilateral idiopathic macular hole （IMH） with normal control group by using optical coherence tomography angiography （OCTA） and investigate its correlationship with the macular blood perfusion. METHODS： We performed a prospective and cross- sectional study that included 19 patients with full-thickness unilateral IMH and 24 age- and sex-matched controls. All participants received OCTA test. The ONH perfusion was evaluated by the regions of peripapillary and whole en face （the sum of peripapillary and optic disc）. The potential correlationship between ONH and parafovea were implied. All the data were performed using the nonparametric test. RESULTS： The mean values of ONH presented that normal control 〉IMH 〉unaffected eyes. A statistical variation was found between three groups in the region of temporal （P=-0.007）, Vessel density notablely decreased on the layers of superficial, deep and choroid of parafovea region in IMH group. The correlative coefficients showed that respectively whole en face and deep retina： r=0.528, peripapillary and deep retina： r=0.525, whole en face and choriocapillaries： r=0.569, peripapillary and choriocapillaries： t=0.504. CONCLUSION： Our study demonstrate a reduced ONH vessel density in both eyes of IMH patients and the vessel density of ONH in IMH eyes are positively correlated with both the retina capillary and choriocapillary in parafoveal. The reduction of vessel densities may indicate the hypoperfusion in IMH eyes,

The correlation between rat retinal nerve fiber layer thickness around optic disc by using optical coherence tomography and histological measurements

·AIM: To explore the correlation between the retinal nerve fiber layer (RNFL) thickness by using optical coherence tomography (OCT) and by histological measurements in normal adult rats and optic nerve transected rats. · METHODS: The RNFL thickness of 36 rats was scanned in a circle 3.46mm far from the optic disc by OCT. The two experimental groups were the normal group ( =20 rats) and the optic nerve transected group ( =16 rats). The latter group included 4 groups ( =4 /group) surviving for 1 day, 3, 5 and 7 days. Then the RNFL thickness of the same retina area was also measured by NF -200 immunohistochemical staining method. Linear regression was used to analyze the correlation between the data obtained from these two methods. ·RESULTS: The RNFL thickness of normal right eyes around optic disc by OCT was 72.35 ±5.71μm and that of the left eyes was 72.65 ±5.88μm ( =0.074). The RNFL thickness of the corresponding histological section by immunohistochemistry was 37.54 ±4.05μm (right eyes) and 37.38 ±4.23μm (left eyes) ( =0.059). There was a good correlation between the RNFL thickness measured by OCT and that measured by histology (R 2 =0.8131). After optic nerve transection, the trend of the RNFL thickness was thinner with the prolonged survival time. The correlation of the thickness detected by the above two methods was approximately (R 2 =0.8265). Value of the RNFL thickness in rats around optic disc measured by OCT was obviously higher than that measured by common histological measurement in normal adult rats and optic nerve transected rats. ·CONCLUSION: The RNFL thickness measured by OCT has a strong correlation with that measured by histological method. Through OCT scanning, we found that the thickness of RNFL gradually becomes thinner in a time-dependent manner.

Spectral domain optical coherence tomography crosssectional image of optic nerve head during intraocular pressure elevation

AIM: To analyze changes of the optic nerve head(ONH) and peripapillary region during intraocular pressure(IOP) elevation in patients using spectral domain optical coherence tomography(SD-OCT).METHODS: Both an optic disc 200×200 cube scan and a high-definition 5-line raster scan were obtained from open angle glaucoma patients presented with monocular elevation of IOP(≥30 mm Hg) using SD-OCT. Additional baseline characteristics included age, gender, diagnosis,best-corrected visual acuity, refractive error, findings of slit lamp biomicroscopy, findings of dilated stereoscopic examination of the ONH and fundus, IOP, pachymetry findings, and the results of visual field.RESULTS: The 24 patients were selected and divided into two groups: group 1 patients had no history of IOP elevation or glaucoma(n =14), and group 2 patients did have history of IOP elevation or glaucoma(n =10). In each patient, the study eye with elevated IOP was classified into group H(high), and the fellow eye was classified into group L(low). The mean deviation(MD)differed significantly between groups H and L when all eyes were considered(P =0.047) and in group 2(P =0.042), not in group 1(P =0.893). Retinal nerve fiber layer(RNFL) average thickness(P =0.050), rim area(P =0.015),vertical cup/disc ratio(P =0.011), cup volume(P =0.028),inferior quadrant RNFL thickness(P =0.017), and clockhour(1, 5, and 6) RNFL thicknesses(P =0.050, 0.012, and0.018, respectively), cup depth(P =0.008), central prelaminar layer thickness(P =0.023), mid-inferior prelaminar layer thickness(P =0.023), and nasal retinal slope(P =0.034)were significantly different between the eyes with groups H and L.CONCLUSION:RNFLaveragethickness,rim area,vertical cup/disc ratio, cup volume, inferior quadrant RNFL thickness, and clock-hour(1, 5, and 6) RNFL thicknesses significantly changed during acute IOP elevation.

Evaluation of optic nerve head vessels density changes after phacoemulsification cataract surgery using optical coherence tomography angiography

·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.

Diagnostic capability of peripapillary retinal nerve fiber layer parameters in time-domain versus spectral-domain optical coherence tomography for assessing glaucoma in high myopia

AIM： To evaluate and compare the diagnostic capabilities of peripapillary retinal nerve fiber layer（p-RNFL） parameters of Spectralis optical coherence tomography（OCT） versus Stratus OCT to detect glaucoma in patients with high myopia. METHODS： This is a retrospective, cross-sectional study. Sixty highly myopic eyes of 60 patients were enrolled, with 30 eyes in the glaucoma group and 30 eyes in the control group. All eyes received peripapillary imaging of the optic disc using Stratus and Spectralis OCT. Areas under the receiver operating characteristic curve（AUROC） and the sensitivity at specificity of 〉80% and 〉95% for p-RNFL parameters obtained using the two devices to diagnose glaucoma were analysed and compared. RESULTS： In Spectralis OCT, p-RNFL thickness parameters with the largest AUROC were the temporal-inferior sector（0.974） and the inferior quadrant（0.951）, whereas in Stratus OCT, the best parameters were the 7-o＇clock sector（0.918） and the inferior quadrant（0.918）. Compared to the Stratus OCT parameters, the Spectralis OCT parameters demonstrated generally higher AUROC; however, the difference was not statistically significant. CONCLUSION： The best p-RNFL parameters for diagnosing glaucoma in patients with high myopia were the temporal-inferior sector on Spectralis OCT and the 7-o＇clock sector on Stratus OCT. There were no significant differences between the AUROCs for Spectralis OCT and Stratus OCT, which suggest that the glaucoma diagnostic capabilities of these two devices in patients with high myopia are similar.

Microperimetry and spectral domain optical coherence tomography in myelinated retinal nerve fibers

Dear Sir,I write to present the correlation between microperimetric （MP） values and the density of myelinated retinal nerve fibers （MNFs） in optical coherence tomography （OCT） imaging.

Influence of corneal power on circumpapillary retinal nerve fiber layer and optic nerve head measurements by spectral-domain optical coherence tomography

AIM：To evaluate the influence of corneal power on circumpapillary retinal nerve fiber layer（cp RNFL）and optic nerve head（ONH）measurements by spectral-domain optical coherence tomography（SD-OCT）.METHODS：Twenty-five eyes of 25 healthy participants（mean age 23.6±3.6y）were imaged by SD-OCT using horizontal raster scans.Disposable soft contact lenses of different powers（from-11 to＋5 diopters including 0diopter）were worn to induce 2-diopter changes in corneal power.Differences in the cp RNFL and ONH measurements per diopter of change in corneal power were analyzed.RESULTS：As corneal power increased by 1 diopter,total and quadrant cp RNFL thicknesses,except for the nasal sector,decreased by-0.19 to-0.32μm（P〈0.01）.Furthermore,the disc,cup,and rim areas decreased by-0.017,-0.007,and-0.015 mm2,respectively（P〈0.001）;the cup and rim volumes decreased by-0.0013 and-0.006 mm3,respectively（P〈0.01）;and the vertical and horizontal disc diameters decreased by-0.006 and-0.007 mm,respectively（P〈0.001）.CONCLUSION：For more precise OCT imaging,the ocular magnification should be corrected by considering both the axial length and corneal power.However,the effect of corneal power changes on cp RNFL thickness and ONH topography are small when compare with those of the axial length.

Optical coherence tomography angiography of the optic nerve head, current situation and future perspective

The circulation of the optic nerve head is derived from two sources;the prelaminar,laminar and retrolaminar circulation are mainly arise from the posterior ciliary artery circulation,whereas the nerve fiber layer over the optic disc is fed by central retinal artery(1,2).A variety of optic neuropathies with ischemic,glaucomatous,inflammatory and hereditary etiologies may affect the

A Prediction Model for Detecting Dysthyroid Optic Neuropathy Based on Clinical Factors and Imaging Markers of the Optic Nerve and Cerebrospinal Fluid in the Optic Nerve Sheath

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.

Effect of a cervical collar on optic nerve sheath diameter in trauma patients

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.

Mesenchymal stem cells for repairing glaucomatous optic nerve

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.

Optic nerve sheath diameters in nontraumatic brain injury:A scoping review and role in the intensive care unit

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.

Neuroinflammation and oxidative stress act in concert to promote neurodegeneration in the diabetic retina and optic nerve:galectin-3 participation

Diabetes is a lifelong disease characterized by glucose metabolic imbalance,in which low insulin levels or impaired insulin signaling lead to hyperglycemic state.Within 20 years of diabetes progression,95%of patients will have diabetic retinopathy,the leading cause of visual defects in working-age people worldwide.Although diabetes is considered a microvascular disease,recent studies have shown that neurodegeneration precedes vascular changes within the diabetic visual system,albeit its mechanisms are still under investigation.Neuroinflammation and oxidative stress are intrinsically related phenomena,since macrophage/microglia and astrocytes are the main sources of reactive oxygen species during central nervous system chronic degenerative diseases,and both pathological processes are increased in the visual system during diabetes.The present review will focus on recent findings of the contribution of oxidative stress derived from neuroinflammation in the early neurodegenerative aspects of the diabetic visual system and their relationship with galectin-3.

Rho/ROCK pathway and neural regeneration: a potential therapeutic target for central nervous system and optic nerve damage

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.

Evoked membrane potential change in rat optic nerve fiber:Computer simulation

Objective The optic nerve is a key component regarding research on visual prosthesis.Previous pharmacological and electrical studies has pinned down the main features of the mechanisms underlying the nerve impulse in the rat optic nerve,and this work proposed a mathematical model to simulate these phenomena.Methods The main active nodal channels：fast Na^＋,persistent Na^,slow K^＋ and a fast repolarizing K^＋（A-current）were added on a double layer representation of the axon.A simplified representation of K^＋ accumulation and clearance in the vicinity of the Ranvier node was integrated in this model.Results The model was able to generate the following features.In the presence of 4-aminopyridine （4-AP）,spike duration increased and a depolarizing afterpotential（DAP）appeared.In the presence of 4-AP and tetraethylammonium（TEA）,the DAP was followed by a hyperpolarizing afterpotential（AHP）and the amplitude of this AHP increased with the frequency of the stimulation.In normal conditions（no drugs）：DAP and AHP were absent after a single action potential（AP）and a short train of AP;there was a relative refractoriness in amplitude lasting for 30 ms after an AP;an early AHP was revealed by a continuous depolarizing current;and there was a partial spike adaptation for a long current step stimulus.Conclusion The model successfully reproduced previous experiments results including long-lasting stimulation experiment,which is known to modify nerve physiological parameter values and is a key issue for visual prosthesis research.

Decellularized optic nerve functional scaffold transplant facilitates directional axon regeneration and remyelination in the injured white matter of the rat spinal cord

Axon regeneration and remyelination of the damaged region is the most common repair strategy for spinal cord injury.However,achieving good outcome remains difficult.Our previous study showed that porcine decellularized optic nerve better mimics the extracellular matrix of the embryonic porcine optic nerve and promotes the directional growth of dorsal root ganglion neurites.However,it has not been reported whether this material promotes axonal regeneration in vivo.In the present study,a porcine decellularized optic nerve was seeded with neurotrophin-3-overexpressing Schwann cells.This functional scaffold promoted the directional growth and remyelination of regenerating axons.In vitro,the porcine decellularized optic nerve contained many straight,longitudinal channels with a uniform distribution,and microscopic pores were present in the channel wall.The spatial micro topological structure and extracellular matrix were conducive to the adhesion,survival and migration of neural stem cells.The scaffold promoted the directional growth of dorsal root ganglion neurites,and showed strong potential for myelin regeneration.Furthermore,we transplanted the porcine decellularized optic nerve containing neurotrophin-3-overexpressing Schwann cells in a rat model of T10 spinal cord defect in vivo.Four weeks later,the regenerating axons grew straight,the myelin sheath in the injured/transplanted area recovered its structure,and simultaneously,the number of inflammatory cells and the expression of chondroitin sulfate proteoglycans were reduced.Together,these findings suggest that porcine decellularized optic nerve loaded with Schwann cells overexpressing neurotrophin-3 promotes the directional growth of regenerating spinal cord axons as well as myelin regeneration.All procedures involving animals were conducted in accordance with the ethical standards of the Institutional Animal Care and Use Committee of Sun Yat-sen University(approval No.SYSU-IACUC-2019-B034)on February 28,2019.

PTEN knockdown with the Y444F mutant AAV2 vector promotes axonal regeneration in the adult optic nerve

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.