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.

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.

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.

Assessment of optic nerve and optic tract alterations in patients with orbital space-occupying lesions using probabilistic diffusion tractography

AIM: To investigate the diffusion changes in both the optic nerve and optic tract in orbital space-occupying lesion patients with decreased visual acuity, and its clinical significance using probabilistic diffusion tractography(PDT). METHODS: Twenty patients with orbital space-occupying lesions and 25 age-and gender-matched healthy persons were included. All patients and controls underwent routine orbital magnetic resonance imaging and diffusion tensor imaging(DTI), using a 3.0 T magnetic resonance scanner(Trio Tim Siemens). After the image data were preprocessed, each DTI parameters of the optic nerve and optic tract was obtained by PDT, including fractional anisotropy(FA), mean diffusivity(MD), axial diffusivity(AD) and radial diffusivity(RD). The asymmetry index(AI) of each parameter was calculated. Compared the parameters of the affected side optic nerve and ipsilateral optic tract with the contralateral side by paired sample t-test;compared AI of parameters of optic nerve and optic tract between the patient group and the control group by independent sample t-test. Patients were divided into threesubgroups according to the low vision grade standard of WHO, compared the FA and AI of FA between the three subgroups by single factor variance analysis. RESULTS: The affected side optic nerve presented significantly decreased FA, increased MD, AD, and RD values compared to the unaffected side(P<0.05). The AI of FA, MD, AD, and RD of optic nerve in the patients was significantly higher than that of the controls(P<0.05). The comparison results of the optic tract showed that there was no significant difference between the patient group and control group in terms of the bilateral optic tracts in patients(P>0.05). The AIs of the FA value of the optic nerve in the eyesight <0.1 subgroup was significantly higher than that in the other groups(P<0.05). CONCLUSION: FA, MD, AD, and RD of the affected side optic nerve of the orbital space-occupying lesions have significantly changed, the FA value is the most sensitive. The PDT could be a useful tool to provide valid quantitative markers of optic nerve injuries and evaluate the severity of orbital diseases, which other examinations cannot be acquired.

The role of monocytes in optic nerve injury

Monocytes,including monocyte-derived macrophages and resident microglia,mediate many phases of optic nerve injury pathogenesis.Resident microglia respond first,followed by infiltrating macrophages which regulate neuronal inflammation,cell proliferation and differentiation,scar formation and tissue remodeling following optic nerve injury.However,microglia and macrophages have distinct functions which can be either beneficial or detrimental to the optic nerve depending on the spatial context and temporal sequence of their activity.These divergent effects are attributed to pro-and anti-inflammatory cytokines expressed by monocytes,crosstalk between monocyte and glial cells and even microglia-macrophage communication.In this review,we describe the dynamics and functions of microglia and macrophages in neuronal inflammation and regeneration following optic nerve injury,and their possible role as therapeutic targets for axonal regeneration.

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.

Changes of optic nerve head microcirculation in high myopia

AIM:To analyze the correlation of age,spherical equivalent(SE),and axial length(AL)with the microcirculation of optic nerve head(ONH)in high myopia(HM).METHODS:In this cross-sectional clinical study,164 right eyes were included.Optical coherence tomography angiography(OCTA)was used to detect ONH vessel density.Eyes were classified based on age,SE,and AL.Groups of Age1,Age2,and Age3 were denoted for age classification(Age1<20y,20y≤Age2<30y,Age3≥30y);Groups SE1,SE2,and SE3 for the SE classification(-9≤SE1<-6 D,-12≤SE2<-9 D,SE3<-12 D);Groups AL1,AL2,AL3,and AL4 for the AL classification(AL1<26 mm,26≤AL2<27 mm,27≤AL3<28 mm,AL4≥28 mm).RESULTS:No significant difference was observed in vessel density among the Age1,Age2,and Age3 groups(all P>0.05)and the SE1,SE2,and SE3 groups(all P>0.05).No significant difference was observed in the intrapapillary vascular density(IVD)among AL1,AL2,AL3,and AL4 groups(P>0.05).However,a significant decrease was found in the peripapillary vascular density(PVD)in the AL1,AL2,AL3,and AL4 groups(F=3.605,P=0.015),especially in the inferotemporal(IT;F=6.25,P<0.001),temporoinferior(TI;F=2.865,P=0.038),and temporosuperior(TS;F=6.812,P<0.001)sectors.The IVD was correlated with age(r=-0.190,P<0.05)but not with SE or AL(P>0.05).The PVD was correlated with AL(r=-0.236,P<0.01)but not with age or SE(P>0.05).CONCLUSION:With the increase of AL,the IVD remains stable while the PVD decreases,especially in the three directions of temporal(IT,TI,and TS).The main cause of microcirculation reduction may be related to AL elongation rather than an increase in age or SE.

Optic nerve injury-induced regeneration in the adult zebrafish is accompanied by spatiotemporal changes in mitochondrial dynamics

Axonal regeneration in the central nervous system is an energy-intensive process.In contrast to mammals,adult zebrafish can functionally recover from neuronal injury.This raises the question of how zebrafish can cope with this high energy demand.We previously showed that in adult zebrafish,subjected to an optic nerve crush,an antagonistic axon-dendrite interplay exists wherein the retraction of retinal ganglion cell dendrites is a prerequisite for effective axonal repair.We postulate a‘dendrites for regeneration’paradigm that might be linked to intraneuronal mitochondrial reshuffling,as ganglion cells likely have insufficient resources to maintain dendrites and restore axons simultaneously.Here,we characterized both mitochondrial distribution and mitochondrial dynamics within the different ganglion cell compartments(dendrites,somas,and axons)during the regenerative process.Optic nerve crush resulted in a reduction of mitochondria in the dendrites during dendritic retraction,whereafter enlarged mitochondria appeared in the optic nerve/tract during axonal regrowth.Upon dendritic regrowth in the retina,mitochondrial density inside the retinal dendrites returned to baseline levels.Moreover,a transient increase in mitochondrial fission and biogenesis was observed in retinal ganglion cell somas after optic nerve damage.Taken together,these findings suggest that during optic nerve injury-induced regeneration,mitochondria shift from the dendrites to the axons and back again and that temporary changes in mitochondrial dynamics support axonal and dendritic regrowth after optic nerve crush.

Selective deletion of zinc transporter 3 in amacrine cells promotes retinal ganglion cell survival and optic nerve regeneration after injury

Vision depends on accurate signal conduction from the retina to the brain through the optic nerve,an important part of the central nervous system that consists of bundles of axons originating from retinal ganglion cells.The mammalian optic nerve,an important part of the central nervous system,cannot regenerate once it is injured,leading to permanent vision loss.To date,there is no clinical treatment that can regenerate the optic nerve and restore vision.Our previous study found that the mobile zinc(Zn^(2+))level increased rapidly after optic nerve injury in the retina,specifically in the vesicles of the inner plexiform layer.Furthermore,chelating Zn^(2+)significantly promoted axonal regeneration with a long-term effect.In this study,we conditionally knocked out zinc transporter 3(ZnT3)in amacrine cells or retinal ganglion cells to construct two transgenic mouse lines(VGAT^(Cre)ZnT3^(fl/fl)and VGLUT2^(Cre)ZnT3^(fl/fl),respectively).We obtained direct evidence that the rapidly increased mobile Zn^(2+)in response to injury was from amacrine cells.We also found that selective deletion of ZnT3 in amacrine cells promoted retinal ganglion cell survival and axonal regeneration after optic nerve crush injury,improved retinal ganglion cell function,and promoted vision recovery.Sequencing analysis of reginal ganglion cells revealed that inhibiting the release of presynaptic Zn^(2+)affected the transcription of key genes related to the survival of retinal ganglion cells in postsynaptic neurons,regulated the synaptic connection between amacrine cells and retinal ganglion cells,and affected the fate of retinal ganglion cells.These results suggest that amacrine cells release Zn^(2+)to trigger transcriptomic changes related to neuronal growth and survival in reginal ganglion cells,thereby influencing the synaptic plasticity of retinal networks.These results make the theory of zinc-dependent retinal ganglion cell death more accurate and complete and provide new insights into the complex interactions between retinal cell networks.

Phosphorylated S6K1 and 4E-BP1 play different roles in constitutively active Rheb-mediated retinal ganglion cell survival and axon regeneration after optic nerve injury

Ras homolog enriched in brain(Rheb) is a small GTPase that activates mammalian target of rapamycin complex 1(mTORC1).Previous studies have shown that constitutively active Rheb can enhance the regeneration of sensory axons after spinal cord injury by activating downstream effectors of mTOR.S6K1 and4E-BP1 are important downstream effectors of mTORC1.In this study,we investigated the role of Rheb/mTOR and its downstream effectors S6K1 and 4E-BP1in the protection of retinal ganglion cells.We transfected an optic nerve crush mouse model with adeno-associated viral 2-mediated constitutively active Rheb and observed the effects on retinal ganglion cell survival and axon regeneration.We found that overexpression of constitutively active Rheb promoted survival of retinal ganglion cells in the acute(14 days) and chronic(21 and 42 days) stages of injury.We also found that either co-expression of the dominant-negative S6K1mutant or the constitutively active 4E-BP1 mutant together with constitutively active Rheb markedly inhibited axon regeneration of retinal ganglion cells.This suggests that mTORC1-mediated S6K1 activation and 4E-BP1 inhibition were necessary components for constitutively active Rheb-induced axon regeneration.However,only S6K1 activation,but not 4E-BP1 knockdown,induced axon regeneration when applied alone.Furthermore,S6K1 activation promoted the survival of retinal ganglion cells at 14 days post-injury,whereas 4E-BP1 knockdown unexpectedly slightly decreased the survival of retinal ganglion cells at 14 days postinjury.Ove rexpression of constitutively active 4E-BP1 increased the survival of retinal ganglion cells at 14 days post-injury.Likewise,co-expressing constitutively active Rheb and constitutively active 4E-BP1 markedly increased the survival of retinal ganglion cells compared with overexpression of constitutively active Rheb alone at 14 days post-injury.These findings indicate that functional 4E-BP1 and S6K1 are neuroprotective and that 4E-BP1 may exert protective effects through a pathway at least partially independent of Rhe b/mTOR.Together,our results show that constitutively active Rheb promotes the survival of retinal ganglion cells and axon regeneration through modulating S6K1 and 4E-BP1 activity.Phosphorylated S6K1 and 4E-BP1 promote axon regeneration but play an antagonistic role in the survival of retinal ganglion cells.

Use of a tissue clearing technique combined with retrograde trans-synaptic viral tracing to evaluate changes in mouse retinorecipient brain regions following optic nerve crush

Successful establishment of reconnection between retinal ganglion cells and retinorecipient regions in the brain is critical to optic nerve regeneration.However,morphological assessments of retinorecipient regions are limited by the opacity of brain tissue.In this study,we used an innovative tissue cleaning technique combined with retrograde trans-synaptic viral tracing to observe changes in retinorecipient regions connected to retinal ganglion cells in mice after optic nerve injury.Specifically,we performed light-sheet imaging of whole brain tissue after a clearing process.We found that pseudorabies virus 724(PRV724)mostly infected retinal ganglion cells,and that we could use it to retrogradely trace the retinorecipient regions in whole tissue-cleared brains.Unexpectedly,PRV724-traced neurons were more widely distributed compared with data from previous studies.We found that optic nerve injury could selectively modify projections from retinal ganglion cells in the hypothalamic paraventricular nucleus,intergeniculate leaflet,ventral lateral geniculate nucleus,central amygdala,basolateral amygdala,Edinger-Westphal nucleus,and oculomotor nucleus,but not the superior vestibular nucleus,red nucleus,locus coeruleus,gigantocellular reticular nucleus,or facial nerve nucleus.Our findings demonstrate that the tissue clearing technique,combined with retrograde trans-synaptic viral tracing,can be used to objectively and comprehensively evaluate changes in mouse retinorecipient regions that receive projections from retinal ganglion cells after optic nerve injury.Thus,our approach may be useful for future estimations of optic nerve injury and regeneration.

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.

Bilateral retinal nerve fiber layer thickness reduction in a 9-year-old myopic boy suffering from unilateral optic neuritis:A case report

BACKGROUND In this paper,we present a 9-year-old boy who demonstrates a complex interplay between myopia progression,axial length(AL)extension,and retinal nerve fiber layer(RNFL)thickness loss in both eyes.Additionally,concurrent optic neuritis has directly impacted RNFL thickness in his right eye,and its potential indirect influence on RNFL and macular ganglion cell layer(mGCL)thickness in his left eye is also noteworthy.CASE SUMMARY A 9-year-old boy with bilateral myopia presented with diminished vision and pain in his right eye due to optic neuritis,while his left eye showed pseudopapilledema.Steroid therapy improved his vision in the right eye,and 16-mo follow-up revealed recovery without recurrence despite myopia progression.Follow-up optical coherence tomography conducted 16 mo later revealed a notable thinning of the RNFL in both eyes,especially along with a reduction in mGCL thickness in the left eye.This intricate interaction between optic neuritis,myopia,and retinal changes underscores the need for comprehensive management,highlighting potential long-term visual implications in young patients.CONCLUSION The progression of myopia and AL extension led to the loss of RNFL thickness in both eyes in a 9-year-old boy.Concurrently,optic neuritis directly affected RNFL thickness in his right eye and may indirectly play a role in the thickness of RNFL and mGCL in his left eye.

Valproate reduces retinal ganglion cell apoptosis in rats after optic nerve crush

The retinal ganglion cells of the optic nerve have a limited capacity for self-repair after injury.Valproate is a histone deacetylase inhibitor and multitarget drug,which has been demonstrated to protect retinal neurons.In this study,we established rat models of optic nerve-crush injury and injected valproate into the vitreous cavity immediately after modeling.We evaluated changes in the ultrastructure morphology of the endoplasmic reticulum of retinal ganglion cells over time via transmission electron microscope.Immunohistochemistry and western blot assay revealed that valproate upregulated the expression of the endoplasmic reticulum stress marker glucose-regulated protein 78 and downregulated the expression of transcription factor C/EBP homologous protein,phosphorylated eukaryotic translation initiation factor 2α,and caspase-12 in the endoplasmic reticulum of retinal ganglion cells.These findings suggest that valproate reduces apoptosis of retinal ganglion cells in the rat after optic nerve-crush injury by attenuating phosphorylated eukaryotic translation initiation factor 2α-C/EBP homologous protein signaling and caspase-12 activation during endoplasmic reticulum stress.These findings represent a newly discovered mechanism that regulates how valproate protects neurons.

Bedside ultrasonography of optic nerve sheath diameter for detection of raised intracranial pressure in nontraumatic neurocritically ill patients

BACKGROUND Delay in treatment of raised intracranial pressure(ICP)leads to poor clinical outcomes.Optic nerve sheath diameter(ONSD)by ultrasonography(US-ONSD)has shown good accuracy in traumatic brain injury and neurosurgical patients to diagnose raised ICP.However,there is a dearth of data in neuro-medical intensive care unit(ICU)where the spectrum of disease is different.AIM To validate the diagnostic accuracy of ONSD in non-traumatic neuro-critically ill patients.METHODS We prospectively enrolled 114 patients who had clinically suspected raised ICP due to non-traumatic causes admitted in neuro-medical ICU.US-ONSD was performed according to ALARA principles.A cut-off more than 5.7 mm was taken as significantly raised.Raised ONSD was corelated with raised ICP on radiological imaging.Clinical history,general and systemic examination findings,SOFA and APACHE 2 score and patient outcomes were recorded.RESULTS There was significant association between raised ONSD and raised ICP on imaging(P<0.001).The sensitivity,specificity,positive and negative predictive value at this cut-off was 77.55%,89.06%,84.44% and 83.82% respectively.The positive and negative likelihood ratio was 7.09 and 0.25.The area under the receiver operating characteristic curves was 0.844.Using Youden’s index the best cut off value for ONSD was 5.75 mm.Raised ONSD was associated with lower age(P=0.007),poorer Glasgow Coma Scale(P=0.009)and greater need for surgical intervention(P=0.006)whereas no statistically significant association was found between raised ONSD and SOFA score,APACHE II score or ICU mortality.Our limitations were that it was a single centre study and we did not perform serial measurements or ONSD pre-and post-treatment or procedures for raised ICP.CONCLUSION ONSD can be used as a screening a test to detect raised ICP in a medical ICU and as a trigger to initiate further management of raised ICP.ONSD can be beneficial in ruling out a diagnosis in a low-prevalence population and rule in a diagnosis in a high-prevalence population.

The mechanism of Chuanxiong Rhizoma on glaucomatous optic nerve injury based on network pharmacology and molecular docking

Based on network pharmacology,this study predicted the potential molecular mechanism and related pathways of the protective effect of traditional Chuanxiong Rhizoma,a traditional Chinese herb,on glaucomatous optic nerve injury,and conducted in vitro experimental verification of the predicted results of network analysis.We analyzed the molecular mechanism of Chuanxiong Rhizoma in the potential treatment of glaucoma by revealing its main active ingredients and predicting its targets,so as to provide reference for subsequent basic research.Network pharmacological research results showed that the potential hub targets and key signaling pathways of Chuanxiong Rhizoma in the treatment of glaucoma were closely related to biological processes such as apoptosis,autophagy,inflammation,oxidative stress and angiogenesis.Molecular docking showed that many active ingredients,such as chrysophanol(CHR),myricanone and retinol,could combine well with their target proteins by intermolecular forces,especially CHR had strong binding ability with each target.We speculated that the main active component of Chuanxiong Rhizoma might be involved in the regulation of PI3K-Akt,Nod-like receptor,IL-4 and IL-13,MAPK,AGE-RAGE and neurotrophin signaling pathway by regulating of PI3K,Akt,TLR4,RAGE,NTRK2 and other key targets.Furthermore,it may achieve multi-directional intervention on apoptosis/autophagy,inflammation/immunity,oxidative stress and nutrient metabolism of axoplasma flow,and then delay the degeneration of optic nerve injury.In vitro experiments showed that the active component CHR of Chuanxiong Rhizoma could reverse the M1-type polarization and autophagy/apoptosis of mouse microglia(BV2)induced by lipopolysaccharide(LPS)at the transcriptional level.Meanwhile,the expression of inflammatory mediators IL-1βand TNF-αwas inhibited,and the mRNA level of anti-inflammatory factor IL-10 was significantly increased.In addition,CHR down-regulates activation of the RAGE-NOX4 pathway mediated by LPS in reducing oxidative stress.In this study,network pharmacology and molecular docking technology were integrated for the first time to explore the potential molecular mechanism of traditional Chinese herb“Chuanxiong Rhizoma”in the treatment on glaucoma,and CHR was innovatively proposed as an important ingredient in Chuanxiong Rhizoma that plays a protective role in the damage of optic nerve.Preliminary verification was conducted through in vitro experiments.The results suggest that Chuanxiong Rhizoma may interfere with autophagy and apoptosis,inhibit immune inflammation,as well as reduce oxidative stress in the treatment of glaucoma through the active components represented by CHR,so as to resist progressive optic nerve injury.Our study provides theoretical basis for the clinical use of Chinese herbal medicine or its extract in glaucoma,and also lays a solid foundation for the research of Chinese medicine in the field of optic nerve protection.

Quantifying peripapillary vessel density and retinal nerve fibre layer in type 1 diabetic children without clinically detectable retinopathy using OCTA

AIM:To quantify changes in radial peripapillary capillary vessel density(ppVD)and the peripapillary retinal nerve fiber layer(pRNFL)in children with type 1 diabetes without clinical diabetic retinopathy by optical coherence tomography angiography(OCTA),providing a basis for early retinopathy in children with type 1 diabetes.METHODS:This was a retrospective study.A total of 30 patients(3–14y)with type 1 diabetes without clinical diabetic retinopathy(NDR group)were included.A total of 30 age-matched healthy subjects were included as the normal control group(CON group).The HbA1c level in the last 3mo was measured once in the NDR group.The pRNFL thickness and ppVD were automatically measured,and the mean pRNFL and ppVD were calculated in the nasal,inferior,temporal,and superior quadrants.The changes in ppVD and pRNFL in the two groups were analyzed.RESULTS:Compared with CON group,the nasal and superior ppVDs decreased in the NDR group(all P<0.01).The thickness of the nasal pRNFL decreased significantly(P<0.01),while the inferior,temporal and superior pRNFLs slightly decreased but not significant in the NDR group(all P>0.05).Person and Spearman correlation analysis of ppVD and pRNFL thickness in each quadrant of the NDR group showed a positive correlation between nasal and superior(all P<0.01),while inferior and temporal had no significant correlation(all P>0.05).There was no significant correlation between the HbA1c level and ppVD and pRNFL in any quadrant(all P>0.05).There was no significant correlation between the course of diabetes mellitus and ppVD and pRNFL in any quadrant(all P>0.05).CONCLUSION:ppVD and pRNFL decrease in eyes of children with type 1 diabetes before clinically detectable retinopathy and OCTA is helpful for early monitoring.

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.

Etomidate affects the anti-oxidant pathway to protect retinal ganglion cells after optic nerve transection

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.