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.

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.

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.

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.

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.

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.

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.

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.

Fiber optic sensing and performance evaluation of a water conveyance tunnel with composite linings under super-high internal pressures

For long-distance water conveyance shield tunnels in operation,the high internal water pressure may cause excessive deformation of composite linings,affecting their structural integrity and serviceability.However,the deformation and failure characteristics of lining structures under internal water pressure are not well investigated in the literature,particularly for three-layer composite linings.This study presents an in situ experimental investigation on the response of two types of composite linings(i.e.separated and combined lining structures)subjected to internal pressures,in which a fiber optic nerve system(FONS)equipped with distributed strain and displacement sensing nerves was employed to monitor the performance of the two composite linings during testing.The experimental results clearly show that the damage of the tunnel lining under different internal pressures was mainly located in the self-compaction concrete layer.The separated lining structure responded more aggressively to the variations in internal pressures than the combined one.Moreover,two evaluation indices,i.e.radial displacement and effective stiffness coefficient,are proposed for describing the changes in the structural bearing performance.The effective stiffness coefficients of the two types of lining structures were reduced by 39.4%and 29.5%,respectively.Considering the convenience of field monitoring,it is suggested that the average strains at different layers can be used as characteristic parameters for estimating the health conditions of lining structures in service.The analysis results provide a practical reference for the design and health evaluation of water conveyance shield tunnels with composite linings.

Structural measurements and vessel density of spectraldomain optic coherence tomography in early,moderate,and severe primary angle-closure glaucoma

AIM:To compare the macular ganglion cell-inner plexiform layer(GCIPL)thickness,retinal nerve fiber layer(RNFL)thickness,optic nerve head(ONH)parameters,and retinal vessel density(VD)measured by spectral-domain optical coherence tomography(SD-OCT)and analyze the correlations between them in the early,moderate,severe primary angle-closure glaucoma(PACG)and normal eyes.METHODS:Totally 70 PACG eyes and 20 normal eyes were recruited for this retrospective analysis.PACG eyes were further separated into early,moderate,or severe PACG eyes using the Enhanced Glaucoma Staging System(GSS2).The GCIPL thickness,RNFL thickness,ONH parameters,and retinal VD were measured by SD-OCT,differences among the groups and correlations within the same group were calculated.RESULTS:The inferior and superotemporal sectors of the GCIPL thickness,rim area of ONH,average and inferior sector of the retinal VD were significantly reduced(all P<0.05)in the early PACG eyes compared to the normal and the optic disc area,cup to disc ratio(C/D),and cup volume were significantly higher(all P<0.05);but the RNFL was not significant changes in early and moderate PACG.In severe group,the GCIPL and RNFL thickness were obvious thinning with retinal VD were decreasing as well as C/D and cup volume increasing than other three groups(all P<0.01).In the early PACG subgroup,there were significant positive correlations between retinal VD and GCIPL thickness(except superonasal and inferonasal sectors,r=0.573 to 0.641,all P<0.05),superior sectors of RNFL thickness(r=0.055,P=0.049).More obvious significant positive correlations were existed in moderate PACG eyes between retinal VD and superior sectors of RNFL thickness(r=0.650,P=0.022),and temporal sectors of RNFL thickness(r=0.740,P=0.006).In the severe PACG eyes,neither GCIPL nor RNFL thickness was associated with retinal VD.CONCLUSION:The ONH damage and retinal VD loss appears earlier than RNFL thickness loss in PACG eyes.As the PACG disease progressed from the early to the moderate stage,the correlations between the retinal VD and RNFL thickness increases.

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.

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.

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.

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.

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.

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.

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.

The concept of gene therapy for glaucoma:the dream that has not come true yet

Gene therapies,despite of being a relatively new therapeutic approach,have a potential to become an important alternative to current treatment strategies in glaucoma.Since glaucoma is not considered a single gene disease,the identified goals of gene therapy would be rather to provide neuroprotection of retinal ganglion cells,especially,in intraocular-pressure-independent manner.The most commonly reported type of vector for gene delivery in glaucoma studies is adeno-associated virus serotype 2 that has a high tro pism to retinal ganglion cells,res ulting in long-term expression and low immunogenic profile.The gene thera py studies recruit inducible and genetic animal models of optic neuropathy,like DBA/2J mice model of high-tension glaucoma and the optic nerve crush-model.Reported gene therapy-based neuroprotection of retinal ganglion cells is targeting specific genes translating to growth factors(i.e.,brain derived neurotrophic factor,and its receptor TrkB),regulation of apoptosis and neurodegeneration(i.e.,Bcl-xl,Xiap,FAS system,nicotinamide mononucleotide adenylyl transferase 2,Digit3 and Sarm1),immunomodulation(i.e.,Crry,C3 complement),modulation of neuroinflammation(i.e.,e rythropoietin),reduction of excitotoxicity(i.e.,Com KIlα)and transcription regulation(i.e.,Max,Nrf2).On the other hand,some of gene therapy studies focus on lowering intra ocular pressure,by impacting genes involved in both,decreasing aqueous humor production(i.e.,aquaporin 1),and increasing outflow facility(i.e.,COX2,prostaglandin F2a receptor,RhoA/RhoA kinase signaling pathway,MMP1,Myocilin).The goal of this review is to summarize the current stateof-art and the direction of development of gene therapy strategies for glaucomatous neuropathy.