The prone position in COVID-19 impacts the thickness of peripapillary retinal nerve fiber layers and macular ganglion cell layers.

The prone position reduces mortality in severe cases of COVID-19 with acute respiratory distress syndrome. However, visual loss and changes to the peripapillary retinal nerve fiber layer (p-RNFL) and the macular ganglion cell layer and inner plexiform layer (m-GCIPL) have occurred in patients undergoing surgery in the prone position. Moreover, COVID-19-related eye problems have been reported. This study compared the p-RNFL and m-GCIPL thicknesses of COVID-19 patients who were placed in the prone position with patients who were not. This prospective longitudinal and case-control study investigated 15 COVID-19 patients placed in the prone position (the "Prone Group"), 23 COVID-19 patients not in the prone position (the "Non-Prone Group"), and 23 healthy, non-COVID individuals without ocular disease or systemic conditions (the "Control Group"). The p-RNFL and m-GCIPL thicknesses of the COVID-19 patients were measured at 1, 3, and 6 months and compared within and between groups. The result showed that the Prone and Non-Prone Groups had no significant differences in their p-RNFL thicknesses at the 3 follow-ups. However, the m-GCIPL analysis revealed significant differences in the inferior sector of the Non-Prone Group between months 1 and 3 (mean difference, 0.74 µm; P = 0.009). The p-RNFL analysis showed a significantly greater thickness at 6 months for the superior sector of the Non-Prone Group (131.61 ± 12.08 µm) than for the Prone Group (118.87 ± 18.21 µm; P = 0.039). The m-GCIPL analysis revealed that the inferior sector was significantly thinner in the Non-Prone Group than in the Control Group (at 1 month 80.57 ± 4.60 versus 83.87 ± 5.43 µm; P = 0.031 and at 6 months 80.48 ± 3.96 versus 83.87 ± 5.43 µm; P = 0.044). In conclusion, the prone position in COVID-19 patients can lead to early loss of p-RNFL thickness due to rising intraocular pressure, which is independent of the timing of prone positioning. Consequently, there is no increase in COVID-19 patients' morbidity burden.

Quantifying Putative Retinal Gliosis in Preclinical Alzheimer's Disease.

Purpose: Neuroinflammation plays a significant role in the pathology of Alzheimer's disease (AD). Mouse models of AD and postmortem biopsy of patients with AD reveal retinal glial activation comparable to central nervous system immunoreactivity. We hypothesized that the surface area of putative retinal gliosis observed in vivo using en face optical coherence tomography (OCT) imaging will be larger in patients with preclinical AD versus controls. Methods: The Spectralis II instrument was used to acquire macular centered 20 × 20 and 30 × 25-degrees spectral domain OCT images of 76 participants (132 eyes). A cohort of 22 patients with preclinical AD (40 eyes, mean age = 69 years, range = 60-80 years) and 20 control participants (32 eyes, mean age = 66 years, range = 58-82 years, P = 0.11) were included for the assessment of difference in surface area of putative retinal gliosis and retinal nerve fiber layer (RNFL) thickness. The surface area of putative retinal gliosis and RNFL thickness for the nine sectors of the Early Treatment Diabetic Retinopathy Study (ETDRS) map were compared between groups using generalized linear mixed models. Results: The surface area of putative retinal gliosis was significantly greater in the preclinical AD group (0.97 ± 0.55 mm2) compared to controls (0.68 ± 0.40 mm2); F(1,70) = 4.41, P = 0.039; Cohen's d = 0.61. There was no significant difference between groups for RNFL thickness in the 9 ETDRS sectors, P > 0.05. Conclusions: Our analysis shows greater putative retinal gliosis in preclinical AD compared to controls. This demonstrates putative retinal gliosis as a potential biomarker for AD-related neuroinflammation.

Molecular mechanism of high glucose-induced mitochondrial DNA damage in retinal ganglion cells.

Mitochondrial DNA damage in retinal ganglion cells (RGCs) may be closely related to lesions of glaucoma. RGCs were cultured with different concentrations of glucose and grouped into 3 groups, namely normal control (NC) group, Low-Glu group, and High-Glu group. Cell viability was measured with cell counting kit-8, and cell apoptosis was measured using flow cytometry. The DNA damage was measured with comet assay, and the morphological changes of damaged mitochondria in RGCs were observed using TEM. Western blot analyzed the expression of MRE11, RAD50, and NBS1 protein. Cell viability of RGCs in Low-Glu and High-Glu groups were lower than that of NC group in 48 and 96 h. The cell apoptosis in NC group was 4.9%, the Low-Glu group was 12.2% and High-Glu group was 24.4%. The comet imaging showed that NC cells did not have tailings, but the low-Glu and high-Glu group cells had tailings, indicating that the DNA of RGCs had been damaged. TEM, mitochondrial membrane potential, ROS, mitochondrial oxygen consumption, and ATP content detection results showed that RGCs cultured with high glucose occurred mitochondrial morphology changes and dysfunction. MRE11, RAD50, and NBS1 protein expression associated with DNA damage repair pathway in High-Glu group declined compared with Low-Glu group. Mitochondrial DNA damage caused by high glucose will result in apoptosis of retinal ganglion cells in glaucoma.

Effect of intravitreal injections due to neovascular age-related macular degeneration on retinal nerve fiber layer thickness and minimum rim width: a cross sectional study.

PURPOSE: The present study tested the hypothesis that repeated anti-VEGF injections are associated with reduced retinal nerve fiber layer (RNFL) and minimum rim width (MRW) of the optic nerve head. PATIENTS AND METHODS: Sixty-six patients with a history of intravitreal injections due to neovascular age-related macular degeneration were included. RNFL and MRW were measured using optical coherence tomography (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany). RESULTS: Mean global RNFL was 90.62 µm and both RNFL as well as MRW significantly decreased with advanced age (p = 0.005 and p = 0.019, respectively). Correlating for the number of injections, no significant impact on RNFL was found globally (p = 0.642) or in any of the sectors. In contrast, however, global MRW was significantly reduced with increasing numbers of intravitreal injections (p = 0.012). The same holds true when adjusted for the confounding factor age (RNFL p = 0.566 and MRW p = 0.023). CONCLUSION: Our study shows that repeated intravitreal injections due to choroidal neovascularization seem to have a deleterious effect on MRW but not on RNFL. This suggests that MRW is a more sensitive marker than RNFL for evaluating the effect of frequent intravitreal injections on the optic nerve head since it seems to be the first structure affected.

TRPV4 antagonist suppresses retinal ganglion cell apoptosis by regulating the activation of CaMKII and TNF-α expression in a chronic ocular hypertension rat model.

Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs), leading to irreversible visual function impairment. Sustained increase in intraocular pressure represents a major risk factor for glaucoma, yet the underlying mechanisms of RGC apoptosis induced by intraocular pressure remains unclear. This study aims to investigate the role of TRPV4 in RGC apoptosis in a rat model of chronic ocular hypertension (COH) and the underlying molecular mechanism. In the COH rat models, we evaluated the visual function, retinal pathological changes and RGC apoptosis. TRPV4 expression and downstream signaling molecules were also detected. We found that RGC density decreased and RGC apoptosis was induced in COH eyes compared with control eyes. TRPV4 expression increased significantly in response to elevated IOP. TRPV4 inhibition by the TRPV4 antagonist HC-067047 (HC-067) suppressed RGC apoptosis and protected visual function. HC-067 treatment upregulated the phosphorylation of CaMKII in both control and COH eyes. Finally, HC-067 treatment suppressed the production of TNF-α induced by ocular hypertension. The TRPV4 antagonist HC-067 might suppress RGC apoptosis by regulating the activation of CaMKII and inhibiting the production of TNF-α in the COH model. This indicated that TRPV4 antagonists may be a potential and novel therapeutic strategy for glaucoma.

Mesenchymal Stromal Cells from Human Wharton's Jelly Modulate the Intraocular Immune Response in a Glucocorticoid Hypertension Model: An Exploratory Analysis.

INTRODUCTION: Glaucoma is a neurodegenerative disease characterized by the loss of retinal ganglion cells. Recent research suggests immunological changes such as cytokine imbalance may affect its pathophysiology. This implies that immunomodulation, like that of mesenchymal cells, could be a potential therapeutic avenue for this disease. However, the effects of intravitreal injections of human Wharton's jelly-derived mesenchymal stromal cells (hWJ-MSCs) on intraocular immune response have not been assessed in ocular hypertension (OH) models. METHODS: We explored this by measuring cytokine levels and expression of other markers, such as glial fibrillary acidic protein (GFAP) and T cells, in 15 randomly divided New Zealand rabbits: G1: OH, G2: hWJ-MSCs, and G3: OH+hWJ-MSCs. We analyzed the aqueous humor (IL-6, IL-8, and TNF-α) and vitreous humor (IFN-γ, IL-10, and TGF-ß) using ELISA and flow cytometry (cell populations), as well as TCD3+, TCD3+/TCD4+, and TCD3+/TCD8+ lymphocytes, and GFAP in the retina and optic nerve through immunohistochemistry. RESULTS: We found a decrease in TNF-α, IL-6, IFN-γ, IL-10, and IL-8 in G3 compared to G1 and an increase in TGF-ß in both G2 and G3. TCD3+ retinal infiltration in all groups was primarily TCD8+ rather than TCD4+ cells, and strong GFAP expression was observed in both the retina and optic nerves in all groups. CONCLUSION: Our results suggest that cellular and humoral immune responses may play a role in glaucomatous optic neuropathy and that intravitreal hWJ-MSCs can induce an immunosuppressive environment by inhibiting proinflammatory cytokines and enhancing regulatory cytokines.

Acquired myelinated retinal nerve fiber layer in a child with neurofibromatosis 1-related optic pathway glioma.

Myelinated retinal nerve fiber layer (RNFL) is a rare structural anomaly that occurs from abnormal myelination extending anterior to the lamina cribrosa. Clinically, myelinated RNFL is characterized as a gray-white lesion with feathered, well-demarcated borders obscuring the retinal vasculature. Myelinated RNFL is typically congenital, benign, and asymptomatic. It is most commonly noted as an incidental finding on ophthalmic examination. However, cases of acquired myelinated RNFL have been reported. We report the case of a patient with neurofibromatosis type 1 and optic pathway glioma with unilateral acquired myelinated RNFL.

Ferroptosis in Glaucoma: A Promising Avenue for Therapy.

Glaucoma, a blind-leading disease largely since chronic pathological intraocular high pressure (ph-IOP). Hitherto, it is reckoned incurable for irreversible neural damage and challenges in managing IOP. Thus, it is significant to develop neuroprotective strategies. Ferroptosis, initially identified as an iron-dependent regulated death that triggers Fenton reactions and culminates in lipid peroxidation (LPO), has emerged as a focal point in multiple tumors and neurodegenerative diseases. Researches show that iron homeostasis play critical roles in the optic nerve (ON) and retinal ganglion cells (RGCs), suggesting targeted treatments could be effective. In glaucoma, apart from neural lesions, disrupted metal balance and increased oxidative stress in trabecular meshwork (TM) are observed. These disturbances lead to extracellular matrix excretion disorders, known as sclerotic mechanisms, resulting in refractory blockages. Importantly, oxidative stress, a significant downstream effect of ferroptosis, is also a key factor in cell senescence. It plays a crucial role in both the etiology and risk of glaucoma. Moreover, ferroptosis also induces non-infectious inflammation, which exacerbate glaucomatous injury. Therefore, the relevance of ferroptosis in glaucoma is extensive and multifaceted. In this review, the study delves into the current understanding of ferroptosis mechanisms in glaucoma, aiming to provide clues to inform clinical therapeutic practices.

Tuberculum meningioma with recovery of glaucoma-like visual field defects after chiasmal decompression: a case report.

BACKGROUND: To report a case of tuberculum meningioma with recovery of glaucoma-like visual field defects after chiasmal decompression. CASE PRESENTATION: A 39-year-old woman presenting with headache was found to have bilateral arcuate retinal nerve fiber layer (RNFL) thinning on optical coherence tomography (OCT) with a corresponding arcuate scotomas consistent with glaucomatous change. However a suprasellar tumor compressing the anterior chiasm from below was found on magnetic resonance imaging of the brain. After resection of the mass, which was diagnosed as meningothelial meningioma by the pathological examination, the glaucoma-like visual field defects resolved despite the RNFL thinning on the OCT showing no improvement. CONCLUSIONS: Chiasmal compression may mimic glaucoma and produce arcuate scotoma rather than temporal visual field loss. There is a possibility that the development of chiasmal compression somehow converted preperimetric glaucoma into a more advanced form accompanied by visual field defects and that the glaucoma reverted to the preperimetric state after chiasmal decompression.

THE EFFECT OF INTERNAL LIMITING MEMBRANE PEELING ON THE INNER RETINAL LAYERS IN PATIENTS WITHOUT MACULAR PATHOLOGIC CONDITION.

BACKGROUND: To examine the effect of internal limiting membrane peeling on the inner retinal layers in patients without macular pathological condition. METHODS: A prospective nonrandomized trial of patients undergoing pars plana vitrectomy with internal limiting membrane peeling for pathologic condition outside the macula was performed. Optical coherence tomography including macular ganglion cell layer, inner plexiform layer, and peripapillary retinal nerve fiber layer imaging was performed before surgery, 1, 3, and 6 months postoperatively, and at the end of follow-up (ranges between 4 and 17 months). Patients with any macular pathological condition on optical coherence tomography before surgery were excluded. The main outcome measure was change in thickness of the ganglion cell layer and inner plexiform layer. RESULTS: Ten patients who underwent pars plana vitrectomy with internal limiting membrane peeling for macula-on retinal detachment were included in the analysis. The mean age was 55 years, and the mean follow up was 10.8 months. All patients completed at least two postoperative follow-up visits that included an optical coherence tomography as per the protocol (range 2-6 months). There was an immediate reduction in the global (G), inferotemporal, superotemporal, and superior (S) ganglion cell layer thickness at the first follow up as compared with the preoperative state ( P = 0.028, P = 0.027, P = 0.026, and P = 0.027 respectively). From the first follow-up visit onward until the final follow-up, the thinning persisted, although there was no further statistically significant thinning. CONCLUSION: Peeling of the internal limiting membrane causes significant ganglion cell layer thinning in maculae without pathologic condition before surgery. At up to 17 months of follow-up, this effect seems to be immediate and nonprogressive.

Clinical Characteristics of Microcystic Macular Edema in Chronic Primary Angle-Closure Glaucoma and Primary Open-Angle Glaucoma Patients.

INTRODUCTION: This study investigated the clinical characteristics of and risk factors for microcystic macular edema (MME) in patients with chronic primary angle-closure glaucoma (CPACG) and primary open-angle glaucoma (POAG). METHODS: This retrospective observational study included 1,588 eyes from 926 glaucoma inpatients and analyzed the patients' basic demographic information, visual field parameters, macular scans, and peripapillary retinal nerve fiber layer thickness. RESULTS: Our findings were that the incidence rate of MME was 3.97% (34/857) in CPACG and 5.88% (43/731) in POAG. MME was predominantly diagnosed at an advanced stage in CPACG (almost 100%) compared to POAG (93.02%). MME was most frequently involved in the inferior (83.12%) quadrant of the peri-macular region in both CPACG and POAG. Risk factors for MME occurrence in CPACG and POAG included lower visual field mean deviation (OR = 1.14, 95%: CI 1.05-1.24, p = 0.003; OR = 1.14, 95% CI: 1.06-1.21, p < 0.001) and younger age (OR = 0.92, 95% CI: 0.88-0.96, p < 0.001; OR = 0.96, 95% CI: 0.93-0.99, p = 0.003), while female sex (OR = 0.30, 95% CI: 0.11-0.84, p = 0.022) reduced the MME occurrence in POAG. CONCLUSION: MME could develop in both CPACG and POAG patients, occurring earlier in POAG. The inferior peri-macular region is commonly affected. Younger age and poorer visual field are risk factors for MME in glaucoma patients.

Interactions of optic radiation lesions with retinal and brain atrophy in early multiple sclerosis.

OBJECTIVE: Retrograde trans-synaptic neuroaxonal degeneration is considered a key pathological factor of subclinical retinal neuroaxonal damage in multiple sclerosis (MS). We aim to evaluate the longitudinal association of optic radiation (OR) lesion activity with retinal neuroaxonal damage and its role in correlations between retinal and brain atrophy in people with clinically isolated syndrome and early MS (pweMS). METHODS: Eighty-five pweMS were retrospectively screened from a prospective cohort (Berlin CIS cohort). Participants underwent 3T magnetic resonance imaging (MRI) for OR lesion volume and brain atrophy measurements and optical coherence tomography (OCT) for retinal layer thickness measurements. All pweMS were followed with serial OCT and MRI over a median follow-up of 2.9 (interquartile range: 2.6-3.4) years. Eyes with a history of optic neuritis prior to study enrollment were excluded. Linear mixed models were used to analyze the association of retinal layer thinning with changes in OR lesion volume and brain atrophy. RESULTS: Macular ganglion cell-inner plexiform layer (GCIPL) thinning was more pronounced in pweMS with OR lesion volume increase during follow-up compared to those without (Difference: -0.82 µm [95% CI:-1.49 to -0.15], p = 0.018). Furthermore, GCIPL thinning correlated with both OR lesion volume increase (ß [95% CI] = -0.27 [-0.50 to -0.03], p = 0.028) and brain atrophy (ß [95% CI] = 0.47 [0.25 to 0.70], p < 0.001). Correlations of GCIPL changes with brain atrophy did not differ between pweMS with or without OR lesion increase ( η p 2 = 5.92e-7 , p = 0.762). INTERPRETATION: Faster GCIPL thinning rate is associated with increased OR lesion load. Our results support the value of GCIPL as a sensitive biomarker reflecting both posterior visual pathway pathology and global brain neurodegeneration.

HLA-Homozygous iPSC-Derived Mesenchymal Stem Cells Rescue Rotenone-Induced Experimental Leber's Hereditary Optic Neuropathy-like Models In Vitro and In Vivo.

BACKGROUND: Mesenchymal stem cells (MSCs) hold promise for cell-based therapy, yet the sourcing, quality, and invasive methods of MSCs impede their mass production and quality control. Induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) can be infinitely expanded, providing advantages over conventional MSCs in terms of meeting unmet clinical demands. METHODS: The potential of MSC therapy for Leber's hereditary optic neuropathy (LHON) remains uncertain. In this study, we used HLA-homozygous induced pluripotent stem cells to generate iMSCs using a defined protocol, and we examined their therapeutic potential in rotenone-induced LHON-like models in vitro and in vivo. RESULTS: The iMSCs did not cause any tumorigenic incidence or inflammation-related lesions after intravitreal transplantation, and they remained viable for at least nine days in the mouse recipient's eyes. In addition, iMSCs exhibited significant efficacy in safeguarding retinal ganglion cells (RGCs) from rotenone-induced cytotoxicity in vitro, and they ameliorated CGL+IPL layer thinning and RGC loss in vivo. Optical coherence tomography (OCT) and an electroretinogram demonstrated that iMSCs not only prevented RGC loss and impairments to the retinal architecture, but they also improved retinal electrophysiology performance. CONCLUSION: The generation of iMSCs via the HLA homozygosity of iPSCs offers a compelling avenue for overcoming the current limitations of MSC-based therapies. The results underscore the potential of iMSCs when addressing retinal disorders, and they highlight their clinical significance, offering renewed hope for individuals affected by LHON and other inherited retinal conditions.

Risk factors associated with progression from papilloedema to optic atrophy: results from a cohort of 113 patients.

BACKGROUND: The aim of this study was to assess the risk factors for atrophic progression of patients with papilloedema secondary to intracranial hypertension, using optical coherence tomography parameters. METHODS: A retrospective study was conducted at Marseille University Hospitals' Ophthalmology departments between December 2015 and December 2021. All patients with papilloedema resulting from elevated intracranial hypertension at the initial presentation were included. Ophthalmological evaluations included analysing retinal nerve fibre layer (RNFL), ganglion cell layer (GCL) and total peripapillary retinal thickness (RT). RESULTS: The study included 222 eyes from 113 patients. The main aetiologies of intracranial hypertension were idiopathic intracranial hypertension (49/113), intracranial tumours (33/113) and cerebral venous thrombosis (15/113). The initial RNFL and RT showed significant correlations with optic atrophy. The mean RNFL was 199.63 µm in the 'no atrophy' group and 365.28 µm in the 'atrophy' group (p<0.001). Similarly, the mean RT was 483.72 µm in the 'non-atrophy' group and 796.69 µm in the 'atrophy' group (p<0.001). The presence of peripapillary haemorrhages showed a strong correlated with optic atrophy with an OR=19.12 (p<0.001). Impaired initial visual acuity was also associated with final optic atrophy with an OR=7.76 (p=0.020). Furthermore, impaired initial GCL was a major predictor of optic atrophy (OR=18.25 (p=0.021)). CONCLUSION: Our study highlights the risk factors for optic atrophy in papilloedema, aiming to facilitate the early detection of patients at a high risk of vision loss and enable more aggressive medical or surgical management.

Therapeutic strategies for glaucoma and optic neuropathies.

Glaucoma is a neurodegenerative eye disease that causes permanent vision impairment. The main pathological characteristics of glaucoma are retinal ganglion cell (RGC) loss and optic nerve degeneration. Glaucoma can be caused by elevated intraocular pressure (IOP), although some cases are congenital or occur in patients with normal IOP. Current glaucoma treatments rely on medicine and surgery to lower IOP, which only delays disease progression. First-line glaucoma medicines are supported by pharmacotherapy advancements such as Rho kinase inhibitors and innovative drug delivery systems. Glaucoma surgery has shifted to safer minimally invasive (or microinvasive) glaucoma surgery, but further trials are needed to validate long-term efficacy. Further, growing evidence shows that adeno-associated virus gene transduction and stem cell-based RGC replacement therapy hold potential to treat optic nerve fiber degeneration and glaucoma. However, better understanding of the regulatory mechanisms of RGC development is needed to provide insight into RGC differentiation from stem cells and help choose target genes for viral therapy. In this review, we overview current progress in RGC development research, optic nerve fiber regeneration, and human stem cell-derived RGC differentiation and transplantation. We also provide an outlook on perspectives and challenges in the field.

TLR4 Inhibition Protects against Retinal Ganglion Cell Damage in Rats with Chronic Ocular Hypertension.

BACKGROUND: This study aims to investigate the protective effect of Toll-like receptor 4 (TLR4) inhibitor Resatorvid (TAK-242) on retinal ganglion cells (RGCs) in a chronic ocular hypertension (COH) rat model, as well as to explore the potential involved mechanisms. METHODS: COH model was built up in rats with a single intracameral administration of cross-linking hydrogel. The expression levels of TLR4, NLR family pyrin domain containing 3 (NLRP3), microglial activation and pro-inflammatory cytokines were evaluated in COH retinas and COH retinas treated with TAK-242 using immunofluorescence staining and Western blot. Additionally, retrograde labeling and neuronal nuclear protein (NeuN) staining were performed to count RGCs. RESULTS: Activated microglia and increased TLR4 expression were observed in the retinas of COH rats. This was accompanied by upregulated expressions of NLRP3, tumor necrosis factor alpha (TNF-α), cytokine interleukin-1ß (IL-1ß) and Interleukin-6 (IL-6). Intravitreal injection of TAK-242 promoted the survival of RGCs by attenuating microglial activation, interfering with the TLR4-NLRP3 pathway and regulating pro-inflammatory cytokines. CONCLUSIONS: Targeting TLR4 inhibition could be a potential therapeutic strategy to protect RGCs from COH damage.

NRF2/ARE mediated antioxidant response to glaucoma: role of glia and retinal ganglion cells.

Glaucoma, the second leading cause of irreversible blindness worldwide, is associated with age and sensitivity to intraocular pressure (IOP). We have shown that elevated IOP causes an early increase in levels of reactive oxygen species (ROS) in the microbead occlusion mouse model. We also detected an endogenous antioxidant response mediated by Nuclear factor erythroid 2-Related Factor 2 (NRF2), a transcription factor that binds to the antioxidant response element (ARE) and increases transcription of antioxidant genes. Our previous studies show that inhibiting this pathway results in earlier and greater glaucoma pathology. In this study, we sought to determine if this endogenous antioxidant response is driven by the retinal ganglion cells (RGCs) or glial cells. We used Nrf2fl/fl mice and cell-type specific adeno-associated viruses (AAVs) expressing Cre to alter Nrf2 levels in either the RGCs or glial cells. Then, we quantified the endogenous antioxidant response, visual function and optic nerve histology after IOP elevation. We found that knock-down of Nrf2 in either cell type blunts the antioxidant response and results in earlier pathology and vision loss. Further, we show that delivery of Nrf2 to the RGCs is sufficient to provide neuroprotection. In summary, both the RGCs and glial cells contribute to the antioxidant response, but treatment of the RGCs alone with increased Nrf2 is sufficient to delay onset of vision loss and axon degeneration in this induced model of glaucoma.

ATP-P2X7R-mediated microglia senescence aggravates retinal ganglion cell injury in chronic ocular hypertension.

BACKGROUND: Dysfunction of microglia during aging affects normal neuronal function and results in the occurrence of neurodegenerative diseases. Retinal microglial senescence attributes to retinal ganglion cell (RGC) death in glaucoma. This study aims to examine the role of ATP-P2X7R in the mediation of microglia senescence and glaucoma progression. METHODS: Forty-eight participants were enrolled, including 24 patients with primary open-angle glaucoma (POAG) and age-related cataract (ARC) and 24 patients with ARC only. We used ARC as the inclusion criteria because of the availability of aqueous humor (AH) before phacoemulsification. AH was collected and the adenosine triphosphate (ATP) concentration was measured by ATP Assay Kit. The chronic ocular hypertension (COH) mouse model was established by microbead occlusion. Microglia were ablated by feeding PLX5622 orally. Mouse bone marrow cells (BMCs) were prepared and infused into mice through the tail vein for the restoration of microglia function. Western blotting, qPCR and ELISA were performed to analyze protein and mRNA expression in the ocular tissue, respectively. Microglial phenotype and RGC survival were assessed by immunofluorescence. The mitochondrial membrane potential was measured using a JC-1 assay kit by flow cytometry. RESULTS: ATP concentrations in the AH were increased in older adults and patients with POAG. The expression of P2X7R was upregulated in the retinal tissues of mice with glaucoma, and functional enrichment analysis showed that P2X7R was closely related to cell aging. Through in vivo and in vitro approaches, we showed that pathological activation of ATP-P2X7R induced accelerated microglial senescence through impairing PTEN-induced kinase 1 (PINK1)-mediated mitophagy, which led to RGC damage. Additionally, we found that replacement of senescent microglia in COH model of old mice with BMCs from young mice reversed RGC damage. CONCLUSION: ATP-P2X7R induces microglia senescence by inhibiting PINK1-mediated mitophagy pathway. Specific inhibition of ATP-P2X7R may be a fundamental approach for targeted therapy of RGC injury in microglial aging-related glaucoma.

The Role of Gut Microbiota in Glaucoma Progression and Other Retinal Diseases.

As a rapidly growing field, microbiota research offers novel approaches to promoting ocular health and treating major retinal diseases, such as glaucoma. Gut microbiota changes throughout life; however, certain patterns of population changes have been increasingly associated with specific diseases. It has been well established that a disrupted microbiome contributes to central nervous system diseases, including Alzheimer disease, Parkinson disease, multiple sclerosis, and glioma, suggesting a prominent role of microbiome in neurodegenerative diseases. This review summarizes the progress in identifying significant changes in the microbial composition of patients with glaucoma by compiling studies on the association between microbiota and disease progression. Of interest is the relationship between increased Firmicutes/Bacteroidetes ratio in patients with primary open-angle glaucoma, increased taurocholic acid, decreased glutathione, and a reduction in retinal ganglion cell survival. Connecting these microbes to specific metabolites sheds light on the pathogenic mechanism and novel treatment strategies. In summary, the current review synthesizes the findings of several studies investigating the effects of shifting bacterial population in retinal diseases, particularly glaucoma, with the aim to identify the current direction of treatment and help direct future endeavors.

Optical coherence tomography detects early optic nerve damage before visual field defect in patients with pituitary tumors.

Optical coherence tomography (OCT) is a useful tool for predicting visual recovery after the removal of pituitary tumors. However, the utility of OCT in patients with pituitary tumors and a normal visual field is unclear. We aimed to analyze OCT features in pituitary tumors without visual field defects. Pituitary tumors without visual field defects were selected. A total of 138 eyes from 69 patients, assessed by the Humphrey visual field test and OCT, were enrolled in this study. Using preoperative coronal sections of MR images, patients were divided into chiasmal compression (CC) and non-chiasmal compression (non-CC) groups, and OCT characteristics were examined. The CC and non-CC groups consisted of 40 and 29 patients, respectively. There were no differences in age, sex, tumor type, or degree of visual field testing, but the tumor size was different between the two groups. On OCT, macular thickness ganglion cell complex (mGCC) was significantly thinner in the CC group than that in the non-CC group (112.5 vs 117.4 um, P < 0.05). Based on a database of healthy participants, 24% and 2% of eyes in the CC and non-CC groups had abnormal mGCC thickness (P < 0.01), respectively. In a sub-analysis of the CC group, patients with an abnormal mGCC thickness were older than a normal one (58.2 vs 41.1 years, p < 0.01). OCT can detect early optic nerve damage due to optic CC by pituitary tumors, even in normal visual fields. The degree of mGCC thinning may provide an appropriate surgical timing for pituitary tumors that compress the optic chiasm.