Acute exposure to air pollutants increase the risk of acute glaucoma.

BACKGROUND: Ambient air pollution is related to the onset and progression of ocular disease. However, the effect of air pollutants on the acute glaucoma remains unclear. OBJECTIVE: To investigate the effect of air pollutants on the incidence of acute glaucoma (acute angle closure glaucoma and glaucomatocyclitic crisis) among adults. METHODS: We conducted a time-stratified case-crossover study based on the data of glaucoma outpatients from January, 2015 to Dec, 2021 in Shanghai, China. A conditional logistic regression model combined with a polynomial distributed lag model was applied for the statistical analysis. Each case serves as its own referent by comparing exposures on the day of the outpatient visit to the exposures on the other 3-4 control days on the same week, month and year. To fully capture the delayed effect of air pollution, we used a maximum lag of 7 days in main model. RESULTS: A total of 14,385 acute glaucoma outpatients were included in this study. We found exposure to PM2.5, PM10, nitrogen dioxide (NO2) and carbon monoxide (CO) significantly increased the odds of outpatient visit for acute glaucoma. Wherein the odds of acute glaucoma related to PM2.5 and NO2 were higher and more sustained, with OR of 1.07 (95%CI: 1.03-1.11) and 1.12 (95% CI: 1.08-1.17) for an IQR increase over lag 0-3 days, than PM10 and CO over lag 0-1 days (OR:1.03; 95% CI: 1.01-1.05; OR: 1.04; 95% CI: 1.01-1.07). CONCLUSIONS: This case-crossover study provided first-hand evidence that air pollutants, especially PM2.5 and NO2, significantly increased risk of acute glaucoma.

Long-term vision outcomes and breed differences of Ahmed Glaucoma Valve implantation in 132 eyes of 122 dogs.

OBJECTIVE: To evaluate the long-term vision outcomes of Ahmed glaucoma valve (AGV) implantation in dogs. PROCEDURES: The medical records of dogs that underwent AGV implantation from January 2010 to December 2019 were reviewed to assess the duration of post-surgical vision preservation (PVP). The relationship between PVP and the underlying cause of glaucoma, implant placement, and preoperative intraocular pressure was evaluated. RESULTS: One hundred and thirty-two eyes of 122 dogs (mean age, 8.3 ± 2.6 years) were included. The mean ± standard error of PVP for all eyes was 57.5 ± 3.9 months. PVP in the dogs with primary acute glaucoma and prior history of cataract surgery was 56.4 ± 4.7 and 59.3 ± 5.9 months, respectively (p = .712). The PVP of the Shiba Inu, American Cocker Spaniel, and other breeds was 63.1 ± 5.5, 33.7 ± 5.3, and 59.1 ± 6.3 months, respectively (p < .05). The PVP in dogs with medial implantation was 61.9 ± 4.7 months, and in those with lateral implantation was 45.4 ± 6.4 months (p = .034). Among the 132 eyes investigated, 48 (36.4%) lost vision by the last follow-up, and 18 eyes retained vision for more than 5 years. Two of the total number of eyes retained their vision for more than 8 years. CONCLUSIONS: The vision outcomes regarding the use of AGV for the management of canine glaucoma were favorable in dogs.

Involvement of the NLRC4 inflammasome in promoting retinal ganglion cell death in an acute glaucoma mouse model.

PURPOSE: To explore the role of nucleotide-binding oligomerization domain-like receptors (NLRs) family caspase-activation and the recruitment domain containing 4 (NLRC4) inflammasome in retinal ganglion cell (RGC) injury induced by an acute glaucoma mouse model. METHOD: A mouse model of acute ocular hypertension, which can lead to retinal ischemia-reperfusion (I/R) injury, was established. The expression level of NLRC4 was detected by polymerase chain reaction and western blotting. Localized expression of NLRC4 was detected by examining immunofluorescence in eyeball sections. Intravitreal adeno-associated virus 2(AAV2) administration was used to knockdown retinal Nlrc4. Fluoro-Gold labeled RGCs and TdT-mediated dUTP nick end labeling were used to evaluate the survival and apoptosis of RGCs. Tlr4-/- mice were utilized to explore whether NLRC4 inflammasome is influenced by Toll-like receptor4 (TLR4). RESULTS: NLRC4, expressed in RGCs and microglial cells, was actively involved in mouse retinal I/R injury. Knockdown of Nlrc4 using an AAV2 vector caused an obvious reduction in the generation of IL-1ß led by the rapidly elevated intraocular pressure, and thereby improved the RGC survival. In addition, activation of the NLRC4 inflammasome could influence the phosphorylation of p38 and Jun N-terminal kinase, which was largely dependent on TLR4 signaling. CONCLUSION: Our study demonstrated the role of NLRC4 inflammasome in promoting RGC damage in mouse retinal I/R injury. Inhibition of NLRC4 might be leveraged as a potential therapeutic target in glaucomatous retinopathy.

Atypical anterior persistent hyperplastic primary vitreous: report of a rare case.

BACKGROUND: Persistent hyperplastic primary vitreous (PHPV) is a congenital form of vitreous dysplasia that can be categorized into anterior, posterior, and mixed types according to the affected location within the eye. Definitive diagnoses of PHPV are usually made based on B-mode ultrasound, optical coherence tomography (OCT), and Doppler ultrasound findings. In this report, we discuss the case of a 7-year-old boy in whom a definitive diagnosis of atypical anterior PHPV was possible based on intraoperative observations, pathological findings, and the results of ophthalmic examination. CASE PRESENTATION: A 7-year-old boy presented with leukocoria and acute glaucoma in his right eye. Imaging suggested characteristics of mixed PHPV. Surgical treatment and pathological examination were performed due to the presence of acute glaucoma and abnormal lens morphology. Typical signs of posterior PHPV (e.g., eyeball shrinkage, the presence of vascular membranes connected to the optic disc, etc.) were not observed. However, there were abundant fibrous vascular membranes around the lens. Pathological examination revealed fibrocyte proliferation in the lens and capsular tissue. Intraoperative findings were used in conjunction with the results of pathological and ophthalmological examinations to make the final diagnosis of anterior PHPV. CONCLUSION: The course and characteristics of PHPV can be unpredictable, and it is often the case that a clear diagnosis cannot be obtained based on clinical characteristics and typical imaging examinations alone. Further surgical treatment and pathological examination may aid in establishing a final diagnosis. In addition to treating the complications of PHPV (e.g., glaucoma), surgery may improve eye appearance and restore visual function to some degree.

Marine-Steroid Derivative 5α-Androst-3ß, 5α, 6ß-triol Protects Retinal Ganglion Cells from Ischemia⁻Reperfusion Injury by Activating Nrf2 Pathway.

High intraocular pressure (IOP)-induced retinal ischemia leads to acute glaucoma, which is one of the leading causes of irreversible visual-field loss, characterized by loss of retinal ganglion cells (RGCs) and axonal injury in optic nerves (ONs). Oxidative stress and the inflammatory response play an important role in the ischemic injury of retinal and optic nerves. We focus on 5α-androst-3ß, 5α, 6ß-triol (TRIOL), a synthetic neuroactive derivative of natural marine steroids 24-methylene-cholest-3ß, 5α, 6ß, 19-tetrol and cholestane-3ß, 5α, 6ß-triol, which are two neuroactive polyhydroxysterols isolated from the soft coral Nephthea brassica and the gorgonian Menella kanisa, respectively. We previously demonstrated that TRIOL was a neuroprotective steroid with anti-inflammatory and antioxidative activities. However, the potential role of TRIOL on acute glaucoma and its underlying mechanisms remains unclear. Here, we report TRIOL as a promising neuroprotectant that can protect RGCs and their axons/dendrites from ischemic-reperfusion (I/R) injury in an acute intraocular hypertension (AIH) model. Intravitreal injection of TRIOL significantly alleviated the loss of RGCs and the damage of axons and dendrites in rats and mice with acute glaucoma. As NF-E2-related factor 2 (Nrf2) is one of the most critical regulators in oxidative and inflammatory injury, we further evaluated the effect of TRIOL on Nrf2 knockout mice, and the neuroprotective role of TRIOL on retinal ischemia was not observed in Nrf2 knockout mice, indicating that activation of Nrf2 is responsible for the neuroprotection of TRIOL. Further experiments demonstrated that TRIOL can activate and upregulate Nrf2, along with its downstream hemeoxygenase-1 (HO-1), by negative regulation of Kelch-like ECH (Enoyl-CoA Hydratase) associated Protein-1 (Keap1). In conclusion, our study shed new light on the neuroprotective therapy of retinal ischemia and proposed a promising marine drug candidate, TRIOL, for the therapeutics of acute glaucoma.

A Novel Synthetic Steroid of 2ß,3α,5α-Trihydroxy-androst-6-one Alleviates the Loss of Rat Retinal Ganglion Cells Caused by Acute Intraocular Hypertension via Inhibiting the Inflammatory Activation of Microglia.

Neuroinflammation has been well recognized as a key pathological event in acute glaucoma. The medical therapy of acute glaucoma mainly focuses on lowering intraocular pressure (IOP), while there are still scarce anti-inflammatory agents in the clinical treatment of acute glaucoma. Here we reported that ß,3α,5α-trihydroxy-androst-6-one (sterone), a novel synthetic polyhydric steroid, blocked neuroinflammation mediated by microglia/macrophages and alleviated the loss of retinal ganglion cells (RGCs) caused by acute intraocular hypertension (AIH). The results showed that sterone significantly inhibited the morphological changes, the up-regulation of inflammatory biomarker ionized calcium-binding adapter molecule 1 (Iba-1), and the mRNA increase of proinflammatory tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) induced by lipopolysaccharide (LPS) in BV2 microglia and RAW264.7 macrophages. Moreover, immunofluorescence and western blotting analysis revealed that sterone markedly abrogated the nuclear translocation and phosphorylation of nuclear factor-κB (NF-κB) p65 subunit. Furthermore, sterone significantly suppressed the inflammatory microglial activation and RGCs' reduction caused by retinal ischemia/reperfusion (I/R) injury in a rat AIH model. These results suggest sterone may be a potential candidate in the treatment of acute glaucoma caused by microglial activation-mediated neuroinflammatory injury.

Trimetazidine protects retinal ganglion cells from acute glaucoma via the Nrf2/Ho-1 pathway.

Acute glaucoma is one of the leading causes of irreversible vision impairment characterized by the rapid elevation of intraocular pressure (IOP) and consequent retinal ganglion cell (RGC) death. Oxidative stress and neuroinflammation have been considered critical for the pathogenesis of RGC death in acute glaucoma. Trimetazidine (TMZ), an anti-ischemic drug, possesses antioxidative and anti-inflammatory properties, contributing to its therapeutic potential in tissue damage. However, the role of TMZ in acute glaucoma and the underlying molecular mechanisms remain elusive. Here, we report that treatment with TMZ significantly attenuated retinal damage and RGC death in mice with acute glaucoma, with a significant decrease in reactive oxygen species (ROS) and inflammatory cytokine production in the retina. Furthermore, TMZ treatment directly decreased ROS production and rebalanced the intracellular redox state, thus contributing to the survival of RGCs in vitro TMZ treatment also reduced the production of inflammatory cytokines in vitro Mechanistically, the TMZ-mediated inhibition of apoptosis and inflammatory cytokine production in RGCs occurred via the regulation of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1/caspase-8 pathway. Moreover, the TMZ-mediated neuroprotection in acute glaucoma was abrogated when an HO-1 inhibitor, SnPP, was used. Our findings identify potential mechanisms of RGC apoptosis and propose a novel therapeutic agent, TMZ, which exerts a precise neuroprotective effect against acute glaucoma.

Proteomic Analysis of Various Rat Ocular Tissues after Ischemia-Reperfusion Injury and Possible Relevance to Acute Glaucoma.

Glaucoma is a group of eye diseases that can cause vision loss and optical nerve damage. To investigate the protein expression alterations in various intraocular tissues (i.e., the cornea, conjunctiva, uvea, retina, and sclera) during ischemia-reperfusion (IR) injury, this study performed a proteomic analysis to qualitatively investigate such alterations resulting from acute glaucoma. The IR injury model combined with the proteomic analysis approach of two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to monitor the protein expression alterations in two groups of specimens (an IR injury group and a control group). The analysis results revealed 221 unique differentially expressed proteins of a total of 1481 proteins in the cornea between the two groups. In addition, 97 of 1206 conjunctival proteins, 90 of 1354 uveal proteins, 61 of 1180 scleral proteins, and 37 of 1204 retinal proteins were differentially expressed. These findings imply that different ocular tissues have different tolerances against IR injury. To sum up, this study utilized the acute glaucoma model combined with 2D-DIGE and MALDI-TOF MS to investigate the IR injury affected protein expression on various ocular tissues, and based on the ratio of protein expression alterations, the alterations in the ocular tissues were in the following order: the cornea, conjunctiva, uvea, sclera, and retina.

Short posterior ciliary artery anatomy in normal and acutely glaucomatous dogs.

OBJECTIVE: To quantify the total number and luminal areas of the short posterior ciliary arteries (SPCA) surrounding the canine optic nerve at the level of the sclera/lamina cribrosa in normal dogs and compare this data to dogs with a history of acute (≤7 days) glaucoma. PROCEDURES: Twelve normal globes were obtained through Harlan Laboratories, the UW-Madison School of Veterinary Medicine necropsy service and via enucleation submissions to the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW). Ten globes with a history of acute glaucoma were obtained from submissions to the COPLOW. Optic nerves were cross-sectioned in 20 micron steps, and five distinct levels were identified: the retinal nerve fiber layer; the retinal pigmented epithelium and neural canal opening; the choroid/pre-lamina; the sclera/lamina cribrosa; and the retro-lamina. At the level of the sclera/lamina cribrosa, SPCA profiles were counted and the luminal area was measured using Cell Sens software. Normal and glaucomatous globes were compared using ANOVA. RESULTS: Statistically significant smaller luminal areas and fewer numbers of arteries were recorded between normal and glaucomatous globes. CONCLUSIONS: The glaucomatous eyes in this study have SPCA with decreased lumina, suggestive of a vascular pathology present at the early stages of clinical glaucoma. Smaller lumina may be a contributing factor to the ischemia, necrosis, and the eventual full-thickness retinal atrophy often seen in glaucomatous dogs.

Insights into Ocular Emergencies: case Series on Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) Secondary to Acute Angle Closure Glaucoma.

This case series aims to report the manifestation of acute secondary optic neuropathy attributed to optic nerve injury associated with a singular episode of markedly elevated intraocular pressure (IOP) during an acute glaucoma attack. The correlation between acute primary angle-closure (APAC) and non-arteritic anterior ischemic optic neuropathy (NAION) remains uncertain within the context of current knowledge. Definitive conclusions regarding the causal relationship between APAC and NAION or their mutual influence cannot be established based on the current evidence. The association between these conditions is recognized as a potential link, and comprehensive research is imperative to elucidate their interrelationship thoroughly. This case series emphasizes the importance of promptly addressing acute optic nerve injury and neuropathy associated with elevated intraocular pressure (IOP) in patients with crowded disc anatomical risk factors. It underscores the need for proactive interventions to prevent irreversible damage, highlighting the infrequent yet vision-compromising occurrence of non-arteritic anterior ischemic optic neuropathy (NAION) in acute primary angle-closure (APAC).

Preoperative Ocular Symptoms Predict Acute Glaucoma After Carotid Revascularization: An Analysis of Combined Single-Center Data and a Systematic Review.

BACKGROUND: Acute glaucoma is a potential complication of carotid revascularization procedures such as endarterectomy or stenting. Although preoperative ocular hypoperfusion may predispose patients to postoperative glaucoma, the details of this complication have not been clarified. METHODS: We retrospectively reviewed the medical records of consecutive patients who underwent carotid revascularization at our institution from January 2019 to December 2022. These patients were divided into glaucoma and nonglaucoma groups. Given the rarity of the event, a systematic literature review was performed to additionally include data from patients who developed acute glaucoma after carotid revascularization. Multivariate logistic regression was performed to identify the risk factors for acute glaucoma. RESULTS: Thirty-five cases, including 2 from our institution, were included in the glaucoma group, and 130 were included in the nonglaucoma group. Most cases (79%) occurred within five days postoperatively. Multivariate analysis revealed that preoperative ocular symptoms were significantly associated with the development of postoperative glaucoma (odds ratio, 361.06; 95% confidence interval, 34.09-3824.27; P < 0.001). Preoperative neovascularization at the iris or anterior chamber angle, indicating severe ocular hypoperfusion, was found in 84% of patients with glaucoma. Permanent visual loss occurred in 41% of patients. The incidence of postoperative glaucoma at our institution was 1.5% (2/132). The positive predictive value of preoperative ocular symptoms for postoperative glaucoma was 0.25 (95% confidence interval, 0.18-0.32). CONCLUSIONS: This study was the first to clarify the risk factors and characteristics of acute glaucoma after carotid revascularization.

Irisin attenuates acute glaucoma-induced neuroinflammation by activating microglia-integrin αVß5/AMPK and promoting autophagy.

Neuroinflammation, characterized by microglial activation and the release of multiple inflammatory mediators, is a key factor in acute glaucomatous injury leading to retinal ganglion cell (RGC) death and ultimately irreversible vision loss. Irisin, a novel exercise-induced myokine, has demonstrated anti-inflammatory activity in ischemia/reperfusion injuries across multiple organs and has displayed a significant neuroprotective role in experimental stroke disease models. This study examined the protective impact of irisin and investigated its potential mechanism involved in this process utilizing an acute ocular hypertension (AOH)-induced retinal injury model in mice and a microglia inflammation model induced by lipopolysaccharide (LPS). There was a transient downregulation of irisin in the retina after AOH injury, with parallel emergence of retinal neuroinflammation and RGC death. Irisin attenuated retinal and optic nerve damage and promotes the phenotypic conversion of microglia from M1 to M2. Mechanistically, irisin significantly upregulated the expression of integrin αVß5, p-AMPK, and autophagy-related markers. Integrin αVß5 was highly expressed on microglia but hardly expressed on RGC. The integrin αVß5 inhibitor cilengitide, the AMPK inhibitor dorsomorphin, and the autophagy inhibitor 3-Methyladenine (3-MA) blocked the neuroprotective effects of irisin. Our results suggest irisin attenuates acute glaucoma-induced neuroinflammation and RGC death by activating integrin αVß5/AMPK in microglia and promoting autophagy. It should be considered a potential neuroprotective therapy for acute glaucoma.

Effect of COVID-19 Shelter-In-Place Orders on Visual Outcomes of Ophthalmic Surgical Emergencies.

PURPOSE: To compare the outcomes of ophthalmic surgical emergencies during shelter-in-place (SIP) order with the corresponding period in 2019. METHODS: This retrospective cohort study compared patients presenting to the Bascom Palmer Eye Institute (BPEI) emergency department (ED) who underwent urgent surgery during the SIP period (March 23-May 17, 2020), compared to the same weeks in 2019 (non-SIP). Main outcome measures included symptom-to-ED time, ED-to-surgical decision time, surgical decision-to-operating room (OR) time, ED-to-OR time, and postoperative follow-up time. Secondary outcome measures included travel distance, visual acuity (VA), intraocular pressure (IOP), and number of glaucoma medications. RESULTS: Seventy-six and 148 patients presented with ophthalmic surgical emergencies in the SIP and non-SIP study periods, respectively. Retinal detachment (RD), acute glaucoma, and open globe injury were the most common diagnoses in both periods. Symptom-to-ED and surgical decision-to-OR times were shorter during the SIP period. SIP patients had comparable preoperative VA but worse postoperative VA compared to non-SIP patients. During the SIP period, RD patients experienced postoperative VA reduction rather than improvement (+0.09 vs. -0.23 logMAR, p = 0.03); glaucoma patients were less likely to reach surgical decision within 24 h (OR 0.16 [95% CI 0.03-0.95]); and globe injuries had longer ED-to-surgical decision time and ED-to-OR time compared to the non-SIP period. Other outcomes were similar between both study periods. CONCLUSION: There was reduced volume of ophthalmic surgical emergencies and worse postoperative vision during SIP compared to the non-SIP period, despite shorter symptom-to-ED and surgical decision-to-OR times suggesting minimal delays in seeking or receiving care.

Early histopathologic changes in the retina and optic nerve in canine primary angle-closure glaucoma.

OBJECTIVE: To characterize the morphology of canine globes enucleated 1-5 days after the onset of overt clinical disease recognized by the owner. PROCEDURES: Paraffin-embedded globes from 47 dogs with acute primary angle-closure glaucoma (PACG) and 10 control dogs free of ocular disease were sectioned in the vertical plane sampling the optic nerve. Hematoxylin and eosin (H&E)-stained sections were used to count ganglion cell numbers. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to quantify cell death, and MHCII immunohistochemistry was used to evaluate for antigen-presenting phagocytes in a smaller subset of cases. RESULTS: MHCII-labeled phagocytes were present in the optic nerve and retina within the first 24 h of documented glaucoma suggesting an early up-regulation. Globes removed within 1 day of overt clinical disease had a mild neutrophilic infiltrate in the retina and optic nerve as well as marked ganglion cell necrosis. By 5 days after clinical signs appear, there is a rapid decline in the number of ganglion cells and cell death detected by TUNEL labeling in the outer and inner nuclear layers of the retina, but not the ganglion cell layer. The neuropil of the optic nerve progresses from edema and neutrophilia to malacia. CONCLUSIONS: These findings suggest that retinal and optic nerve degeneration in dogs with PACG progresses rapidly to irreversible tissue loss within days of recognizable clinical disease.

Low ambient temperature and temperature drop as novel risk factors of acute glaucoma: a case-crossover study.

The prevalence of glaucoma has seasonal variation in population, but the role of ambient temperature and its variation remains unclear in this seasonal trend. So, we conducted a time-stratified case-crossover study to examine the association of ambient temperature and temperature change between neighboring days (TCN) with the risk of acute glaucoma. Data on meteorological parameters and glaucoma outpatient visit between 2015 and 2021 covered all districts of Shanghai. Conditional logistic regression with distributed lag nonlinear model was applied to estimate the association of temperature or TCN with the risk of acute glaucoma. A total of 7,746 patients diagnosed with acute primary angle-closure glaucoma (APACG) were included in this analysis. We observed a significant increase in the risk of acute glaucoma with cold temperature and temperature drop. Compared with the referent temperature (32℃), moderate low (12 °C) and extreme low (4 °C) temperature exposures were associated with higher risk of acute glaucoma outpatient visit, with the highest cumulative OR of 1.46 (95% CI: 1.11, 1.91) and 1.50 (95% CI: 1.09, 2.06) over lag 0-2 days. Temperature drop (TCN = - 4 °C) also increases the risk of acute glaucoma (OR = 1.34, 95% CI: 1.07, 1.67) over lag 0-7 days, comparing with no temperature change. Patients of female and above age 65 were more vulnerable to cold exposure and temperature drop. This case-crossover study provided novel and robust individual-level evidence that low ambient temperature and temperature drop significantly increase the acute glaucoma risk. The findings provide protective strategies for glaucoma patient, especially for female and the old, under cold exposure and sudden temperature decline.

Fermented maize slurry (Ogi) and its supernatant (Omidun) mitigate elevated intraocular pressure by modulating BDNF expression and glial plasticity in the retina-gut axis of glaucomatous rats.

OBJECTIVES: Growing interest has been reported on the health benefits of fermented foods, which includes cognition enhancement and inflammation attenuation. BDNF is a known protectant against retinal degeneration, however, therapies that target this neurotrophic factor has been limited. Therefore, we assessed the reaction of BDNF and glial cells in glaucomatous rats and their response to treatment with fermented maize products. METHODS: Thirty male adult rats were either injected via the episcleral vein with hypertonic saline to elevate intraocular pressure (IOP) or treated with fermented maize slurry (Ogi) or its supernatant (Omidun). Following sacrifice, the retina and duodenum were studied by immunohistochemical analysis using antibodies directed against GFAP, AIF-1 and BDNF. RESULTS: Hypertonic saline injection produced hypertrophy of the Müller cells and increased GFAP and AIF-1 expression in the retina and gut when compared to the control. Treatment with Ogi and Omidun produced varying degrees of reduction of gliosis, protection against hypertonic saline-induced retinal ganglion cell loss, and reduced intraocular pressure. BDNF expression was downregulated following the hypertonic saline assault, while Omidun and Ogi treatment abrogated its reduction following the hypertonic saline assault. CONCLUSIONS: Collectively, our findings suggest that acute elevation of IOP alters crosstalk between gut and retina with consequent aberrant activation of glial cells; and that probiotic bacteria like the lactic acid bacteria rich in fermented foods including Ogi and Omidun may offer neuroprotection to the ganglionic cells by attenuating the retinal glial reaction and improving BDNF activity.

Bilateral acute angle closure after venlafaxine intake in a young patient with a narrow iridocorneal angle.

We report a case of bilateral and acute angle closure after a single dose of antidepressant venlafaxine in a 40-year-old woman with no previous pathologies, who asked for consultation for blurred vision and pain in the left eye. Initial evaluation included visual acuity, slit lamp biomicroscopy and intraocular pressure (IOP) measurement using Goldmann's applanation tonometer. Gonioscopy and fundus examination were also performed in both eyes. Examination and IOP supported the diagnosis of acute glaucoma in the left eye. The patient's evolution was satisfactory after bilateral peripheral iridotomy was performed with Nd-YAG laser, as described in the cases reported in the international literature. The pathophysiology of angle closure and its relationship with venlafaxine intake were also discussed.

Astaxanthin protects retinal ganglion cells from acute glaucoma via the Nrf2/HO-1 pathway.

The death of retinal ganglion cells (RGCs) during acute glaucoma causes progressive degeneration of the retinal nerve and irreversible blindness. Astaxanthin (AST) is a type of xanthophyll carotenoids and naturally synthesized by multiple halobios. It has been reported to protect the retina from acute glaucoma due to its anti-oxidative and anti-neuroinflammatory properties. However, the mechanism underlying this process remains unclear. We designed a mouse model with acute glaucoma and AST was administered by oral gavage. Hematoxylin and eosin staining was utilized to evaluate the condition of retina and the number of ganglion cells was counted. QRT-PCR was performed to evaluate the mRNA levels of Bax and Bcl2 while Western blot assay was used to determine the protein levels of Bax, Bcl2, Nrf2 and HO-1. AST protected the retinal integrity of mice with acute glaucoma. The apoptosis of RGCs induced by ischemia and reperfusion was repressed by AST. The protective functions of AST on the retinal and ganglion cells decreased with the knock-down of Nrf2. AST promoted the activation of Nrf2 and Ho-1 in the RGCs of the model mice. AST protected the RGCs from apoptosis during acute glaucoma and alleviated the severe retinopathy symptoms through the Nrf2/Ho-1 pathway.

NLRP12 collaborates with NLRP3 and NLRC4 to promote pyroptosis inducing ganglion cell death of acute glaucoma.

BACKGROUND: Acute glaucoma, characterized by a sudden elevation in intraocular pressure (IOP) and retinal ganglion cells (RGCs) death, is a major cause of irreversible blindness worldwide that lacks approved effective therapies, validated treatment targets and clear molecular mechanisms. We sought to explore the potential molecular mechanisms underlying the causal link between high IOP and glaucomatous RGCs death. METHODS: A murine retinal ischemia/ reperfusion (RIR) model and an in vitro oxygen and glucose deprivation/reoxygenation (OGDR) model were used to investigate the pathogenic mechanisms of acute glaucoma. RESULTS: Our findings reveal a novel mechanism of microglia-induced pyroptosis-mediated RGCs death associated with glaucomatous vision loss. Genetic deletion of gasdermin D (GSDMD), the effector of pyroptosis, markedly ameliorated the RGCs death and retinal tissue damage in acute glaucoma. Moreover, GSDMD cleavage of microglial cells was dependent on caspase-8 (CASP8)-hypoxia-inducible factor-1α (HIF-1α) signaling. Mechanistically, the newly identified nucleotide-binding leucine-rich repeat-containing receptor (NLR) family pyrin domain-containing 12 (NLRP12) collaborated with NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing protein 4 (NLRC4) downstream of the CASP8-HIF-1α axis, to elicit pyroptotic processes and interleukin-1ß (IL-1ß) maturation through caspase-1 activation, facilitating pyroptosis and neuroinflammation in acute glaucoma. Interestingly, processing of IL-1ß in turn magnified the CASP8-HIF-1α-NLRP12/NLRP3/NLRC4-pyroptosis circuit to accelerate inflammatory cascades. CONCLUSIONS: These data not only indicate that the collaborative effects of NLRP12, NLRP3 and NLRC4 on pyroptosis are responsible for RGCs death, but also shed novel mechanistic insights into microglial pyroptosis, paving novel therapeutic avenues for the treatment of glaucoma-induced irreversible vision loss through simultaneously targeting of pyroptosis.

Spontaneous malignant glaucoma: Case report and review of the literature.

Malignant glaucoma usually occurs after anterior segment surgery (typically after glaucoma surgery). The aim of this article is to report a case of spontaneous malignant glaucoma (SpMG), which required phacovitrectomy for resolution and to review the cases of SpMG reported in modern literature. Only nine cases were identified. SpMG has no gender predilection and age at onset seems to be lower (mean age 47 years) than in secondary malignant glaucoma (SeMG). Nearly in half of the reported patients (4 out of 9) the condition had a bilateral presentation. The risk factors that have been identified for SeMG (nanophthalmos, shallow anterior chamber, iris plateau, zonular laxity) are underrepresented in SpMG.