Search Results (148)

Glaucoma, a leading cause of irreversible visual impairment, is driven by progressive retinal ganglion cell (RGC) degeneration. Emerging evidence highlights astrocytes as pivotal players in its pathogenesis, with their heterogeneity and pathological metabolic reprogramming profoundly impacting RGC survival. This review synthesizes current insights into astrocyte diversity and metabolic alterations during glaucoma-related RGC injury, emphasizing molecular mechanisms from proteomic studies. Key focuses include fatty acid metabolism, neuroinflammation, and signaling pathways that modulate astrocyte function and contribute to neurodegeneration. Despite advances, challenges remain—particularly in characterizing astrocyte subtypes and identifying actionable targets within astrocyte-mediated metabolic/inflammatory cascades. By unraveling the interplay between astrocyte heterogeneity, metabolic reprogramming, and RGC vulnerability, this review provides novel theoretical frameworks to inform targeted glaucoma therapies. Full article

Oxidative stress is a key contributing and convergent pathogenic mechanism linked to retinal and optic nerve diseases including age-related macular degeneration, diabetic retinopathy, and glaucoma. The retina is highly susceptible to redox imbalance due to intense mitochondrial activity, oxygen consumption, and light exposure. While endogenous drivers are well recognized, the contribution of environmental exposure to retinal oxidative injury remains incompletely defined. This review uniquely integrates emerging environmental contaminants with canonical oxidative stress pathways. We examine how cigarette smoke, ultraviolet radiation, heavy metals, microplastics, and per- and polyfluoroalkyl substances (PFASs) promote oxidative injury through mitochondrial dysfunction, inflammatory signaling, impaired antioxidant responses, and ferroptotic pathways. We also highlight therapeutic strategies targeting oxidative pathways and emphasize the importance of exposure-informed retinal and optic nerve disease research. Full article

Glaucoma is no longer viewed solely as a pressure-mediated optic neuropathy but as a chronic neurodegenerative disease with a strong immune component. Across experimental models and patient samples, convergent inflammatory circuitry complement activation, NLRP3 inflammasome signaling, and microglial reactivity emerge as a central driver of retinal ganglion cell (RGC) dysfunction and death. Local complement upregulation (C1q, C3, C5) in the retina and optic nerve head (ONH) promotes aberrant synaptic tagging, phagoptosis, and membrane attack complex stress. In parallel, biomechanical strain, ischemia, mitochondrial damage, and danger-associated molecular patterns prime and activate the NLRP3 inflammasome in microglia, astrocytes, and ONH cells, leading to caspase-1 activation, IL-1β/IL-18 maturation, and pyroptotic or apoptotic injury. Microglia integrate these cues, shifting from early protective surveillance to chronic maladaptive states that amplify complement and inflammasome outputs. This review synthesizes mechanistic links within the complement NLRP3 microglia axis, considers systemic and adaptive immune contributions, and proposes a translational framework for immune-based clinical stratification. The literature for this review was identified through searches of PubMed, Web of Science, and Scopus using combinations of the terms ‘glaucoma’, ‘complement’, ‘inflammasome’, ‘NLRP3’, ‘microglia’, and ‘neuroinflammation’. Priority was given to recent experimental, translational, and clinical studies. We then evaluate emerging immunomodulatory therapies, complement inhibitors, inflammasome blockers, microglial state reprogrammers, cytokine biologics, and cell-derived immunoregulatory approaches, highlighting biomarkers and trial design needs. An immune systems view of glaucoma enables precision neuroprotection for patients who progress despite controlled intraocular pressure. Full article

Glaucoma is increasingly recognized as an ischemic neurodegenerative disorder that extends beyond elevated intraocular pressure (IOP) to involve complex vascular, metabolic, and inflammatory mechanisms. Retinal ganglion cells are particularly vulnerable to ischemia–reperfusion injury, oxidative stress, and chronic neuroinflammation, leading to progressive disconnection from central visual pathways. Current therapies primarily target IOP reduction but fail to address ischemia-driven neurodegeneration or to restore lost neuronal connectivity. Ischemia triggers excitotoxicity, oxidative stress, and a maladaptive inflammatory response involving activated microglia and astrocytes, perpetuating neuronal injury and suppressing intrinsic regenerative capacity. Thus, restoring neural plasticity and mitigating neuroinflammation represent key unmet therapeutic needs. Psychoplastogens are a class of compounds capable of rapidly enhancing structural and functional neuroplasticity and have recently emerged as promising multitarget agents. Compounds such as ketamine, psilocybin, N,N-dimethyltryptamine (DMT), and some newly synthesized non-hallucinogenic analogs act through convergent signaling pathways involving BDNF–TrkB–mTOR, promoting dendritic growth, synaptogenesis, and glial modulation. Beyond their neurotrophic effects, psychoplastogens seem to exert potent immunomodulatory actions. In this review we will explore the interplay between ischemia, neurodegeneration, neuroinflammation, and impaired plasticity in glaucoma, integrating mechanistic insights from cerebral ischemia. We discuss emerging preclinical evidence supporting psychoplastogens as neurorestorative and anti-inflammatory agents, propose their potential application in ocular ischemic neurodegeneration, and outline translational challenges for future studies. Full article

Background: Glaucoma is a neurodegenerative disease and the second leading cause of irreversible blindness in developed countries. It is characterized by progressive loss of retinal ganglion cells (RGCs) and optic nerve axons, leading to permanent vision impairment. Although elevated intraocular pressure (IOP) is the main recognized risk factor, recent evidence suggests that ocular and gut microbiota may play a significant role in the onset and progression of glaucoma. Objectives: This study aimed to characterize ocular and gut microbiota alterations in patients with different types of glaucoma. Methods: Five searches were conducted between June and September 2025 using selected keywords. A total of 121 articles were identified, of which 14 met the inclusion criteria following the PRISMA 2020 guidelines. Results: Findings indicate a Mendelian genetic predisposition influencing microbiota composition associated with glaucoma development. Patients treated with benzalkonium chloride (BAK) showed increased Gram-negative and Alphaproteobacteria on the ocular surface, along with enhanced lipopolysaccharide synthesis. Compared with controls, glaucoma patients exhibited reduced Corynebacterium mastiditis and Actinobacteria and increased Firmicutes, Proteobacteria, and Verrucomicrobiota. Dysbiosis was more pronounced in patients with concurrent dry eye disease, characterized by higher Gram-negative taxa and pro-inflammatory microbial activity. Conclusions: Significant differences in ocular and gut microbiota were observed between glaucoma patients and controls, as well as among glaucoma subtypes such as pseudoexfoliation and primary open-angle glaucoma. Age-related dysbiosis and epigenetic factors appear to contribute to disease development. Microbiota profiling may offer new opportunities for improved prediction, management, and treatment of glaucoma. Full article

Ocular diseases, including glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD), remain major global causes of irreversible vision loss. Despite advances in clinical management, current therapies insufficiently address the shared metabolic, inflammatory, vascular, and neurodegenerative mechanisms underlying these conditions. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for type 2 diabetes and obesity, have emerged as multi-target candidates for ocular therapeutics due to their pleiotropic anti-inflammatory, antioxidant, vasculoprotective, and neuroprotective properties. Preclinical studies consistently demonstrate that GLP-1RAs preserve blood–retina barrier integrity, suppress pathological angiogenesis, mitigate oxidative and inflammatory stress, and protect retinal neurons from degeneration. Complementary clinical and real-world evidence shows a robust and reproducible reduction in glaucoma risk among GLP-1RA users across diabetic and non-diabetic populations. By contrast, findings for DR and AMD are more heterogeneous and appear context-dependent, with potential benefits most evident in early or non-exudative disease stages. Emerging safety considerations—including reports of nonarteritic anterior ischemic optic neuropathy and early DR worsening in the setting of rapid glycemic improvement—highlight the need for careful interpretation, individualized risk assessment, and appropriate ophthalmic monitoring. This review synthesizes molecular mechanisms, experimental data, clinical and pharmacoepidemiologic evidence, and safety signals to critically evaluate the therapeutic potential of GLP-1RAs in ocular disease. We also outline key translational challenges, including the need for ocular-targeted delivery strategies, prospective ophthalmology-specific trials, and precision-medicine approaches to determine when and how GLP-1RAs can be safely advanced as disease-modifying treatments in ophthalmology. Full article

Glaucoma progression differs markedly between individuals despite comparable intraocular pressure control, implying additional modifiable contributors to neurodegeneration. We evaluated the joint impact of sleep deficit and inflammatory cytokine trajectories on retinal nerve fiber layer (RNFL) loss. In this 24-month prospective longitudinal observational cohort, 57 participants (19 controls, 19 prostaglandin-treated glaucoma, 19 untreated glaucoma) underwent spectral-domain OCT, validated sleep assessment, and serial IL-6 and TNF-α profiling. Longitudinal models tested independent and interactive effects of sleep deficit and inflammation on RNFL change, and mediation analyses assessed whether inflammation explains the sleep–progression association. RNFL loss rates were −0.20 ± 0.10 μm/year (controls), −1.06 ± 0.89 μm/year (treated), and −1.94 ± 0.78 μm/year (untreated; p < 0.001). Sleep deficit correlated with RNFL loss in glaucoma (r = −0.41, p = 0.010) but not controls, with stronger effects in untreated disease (p = 0.034). Each hour of sleep deficit was associated with 0.09–0.11 μm/year faster RNFL loss (p < 0.05). A combined sleep–inflammation model improved risk stratification (C-statistic = 0.68). Mediation was not supported. Sleep deficit and inflammatory cytokines act as parallel, independent risk factors for glaucoma progression. Integrating sleep and inflammatory profiling may enhance personalized risk assessment beyond pressure-based management. Full article

Brimonidine, a highly selective α₂-adrenergic receptor agonist originally developed for glaucoma treatment, has emerged as an important dermatological agent due to its potent vasoconstrictive and anti-inflammatory properties. This review summarizes its pharmacological characteristics, and clinical applications. By activating α₂-adrenergic receptors in cutaneous vessels, brimonidine induces rapid, reversible vasoconstriction and reduces neurogenic inflammation, leading to significant improvement of facial erythema in rosacea. Beyond its approved indication, topical brimonidine demonstrates efficacy in alcohol flushing syndrome, telangiectasia, post-procedural erythema, and as a local hemostatic agent in dermatologic surgery. Its favorable safety profile and minimal systemic absorption make it suitable for long-term use, though transient rebound erythema may occur. Advances in nanotechnology—such as supramolecular hydrogels and lipid-based carriers—enhance skin retention, prolong therapeutic action, and improve tolerability. These developments, together with ongoing synthesis of new quinoxaline–imidazoline analogues, open prospects for next-generation α₂-agonists with optimized selectivity and dermatologic applicability. Brimonidine’s emerging role extends to dermatologic formulations for transient redness and sensitive skin management. Integrating pharmacological, formulation, and molecular insights may transform brimonidine from a niche rosacea therapy into a versatile platform for vascular, inflammatory, and aesthetic skin treatments. Full article

Background: Aloe vera gel in 0.3% hyaluronate (AV/HA) could mitigate glaucoma therapy-related ocular surface disease (GTOSD). Methods: Thirty-nine patients diagnosed with GTOSD and receiving AV/HA or HA underwent ocular surface disease index (OSDI), Symptom Assessment iN Dry Eye (SANDE), National Eye Institute Visual Function Questionnaire (NEI VFQ)-25 questionnaires, and tear matrix metalloproteinase-9 (MMP-9), break-up time (BUT), corneal fluorescein staining (CFS), Schirmer test I (STI), and bulbar conjunctival hyperemia (BCH) determination. Results: After one month, AV/HA increased BUT (5 (7–4.5) to 7 (8–5.5)) and STI (12 (19.5–8) to 13.5 (20–10)), while it decreased BCH (2.2 (2.3–1.3) to 2.1 (2.2–1.2)) and CFS (3 (4–2) to 2 (3.0–1.5)) (p < 0.001). SANDE and OSDI scores were reduced from 36.18 (38.5–20.5) to 22.91 (31.5–17.21), and 29.5 (32.5–19.5) to 20 (26.5–18) (p < 0.001). HA reduced BCH from 2.75 (3.20–2.15) to 2.25 (2.30–1.90) (p = 0.014) and CFS from 3.5 (5–2.75) to 2.5 (4–2) (p = 0.014), while it increased BUT (p = 0.036). The SANDE score decreased from 28.95 (47.6–20.9) to 26.86 (36.41–19.90) (p = 0.009), whereas the OSDI decreased from 40 (49–19.5) to 29 (42–19.75) (p = 0.005). Any significant change in NEI VFQ-25 was collected. A trend for an MMP-9 immunoassay positivity reduction was observed in AV/HA (0.073). Conclusions: These findings invite considering lubricants enriched with natural anti-inflammatory agents, such as Aloe vera, as a potential adjunctive option to improve the ocular surface in glaucoma. Full article

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder in which ocular involvement represents a clinically significant yet frequently underrecognized contributor to morbidity. Ocular manifestations in SLE may arise from disease activity itself, but also as adverse effects of long-term pharmacological therapy. With the advent of targeted immunomodulatory agents, the therapeutic landscape of SLE has expanded beyond conventional drugs such as hydroxychloroquine and corticosteroids toward biologics and small molecules designed to interfere with specific immunological pathways. These advances have improved systemic disease control and survival; however, their ophthalmological safety profiles remain only partially defined. This review synthesizes current evidence on ocular adverse events associated with both traditional and emerging SLE therapies. Established agents, particularly hydroxychloroquine and corticosteroids, are consistently linked to complications including retinopathy, posterior subcapsular cataracts, steroid-induced glaucoma, and central serous chorioretinopathy. In contrast, recently approved or investigational therapies—such as belimumab, anifrolumab, voclosporin, dual BAFF/APRIL inhibitors, rituximab, JAK inhibitors, CD40/CD40L blockade, CD38 inhibition, and mesenchymal stromal cell-based strategies—have limited but evolving safety data, with potential ocular adverse events spanning inflammatory, vascular, neuro-ophthalmic, and structural domains. Although ocular complications appear infrequent in clinical trials, underdetection in real-world practice and insufficient long-term monitoring may underestimate their true incidence. These findings highlight the need for systematic ophthalmological surveillance in patients receiving immunomodulatory therapies for SLE. Early recognition and timely management of ocular toxicity are crucial to safeguarding visual function and optimizing long-term therapeutic outcomes in this vulnerable patient population. Full article

This study investigated the region-specific roles of transforming growth factor-β2 (TGF-β2) and angiotensin II (AngII) in extracellular matrix (ECM) remodeling and inflammatory responses within scleral tissues surrounding the optic nerve head (ONH), using primary human fibroblasts from posterior sclera, peripapillary sclera (ppScl), and fibroblast-like cells from lamina cribrosa (LC). In vivo validation was performed in a chronic ocular hypertension rat model. Fibrotic and inflammatory markers were analyzed by Western blotting, quantitative PCR, and immunocytochemistry following TGF-β2 or AngII stimulation, and in vivo effects were assessed after subtenon injection of pathway-specific inhibitors. TGF-β2 induced robust upregulation of α-smooth muscle actin, collagen type I, and fibronectin across all scleral regions, whereas AngII elicited regionally confined pro-inflammatory responses, particularly in the LC and ppScl, characterized by increased cyclooxygenase-2 expression. Inhibition of either pathway reduced ECM deposition in vivo, but only AngII blockade significantly attenuated glial activation and preserved retinal ganglion cells. These findings demonstrate that TGF-β2 predominantly drives fibrosis, while AngII promotes region-specific neuroinflammation, and that inflammation, rather than fibrosis alone, plays a critical role in glaucomatous neurodegeneration. Targeting both fibrotic and inflammatory mechanisms in a region-specific manner may offer improved neuroprotection in glaucoma. Full article

Objectives: We aimed to determine if a 2-week pre-operative course of fluorometholone (FML) eyedrops in chronically medicated glaucoma patients reduces the levels of the pro-inflammatory cytokine Monocyte Chemoattractant Protein 1 (MCP-1) and improves early post-operative outcomes after trabeculectomy or phaco-trabeculectomy. Methods: We conducted a single-center, unmasked, prospective pilot interventional case series of 36 patients with glaucoma who received a 2-week course of FML eyedrops prior to undergoing trabeculectomy. A multiplex bead assay was used to quantify the presence of MCP-1 levels in tear samples before and after the use of FML eyedrops, and 307 eyes without treatment with topical FML served as historical controls. Clinical outcome measures of early post-operative outcomes included IOP and additional post-operative interventions (i.e., needling, glaucoma medications, and surgery) required to achieve the desired IOP at 6 months. Results: Out of 36 patients who received FML, 19 patients had a low MCP-1 level (<250 pg/mL/mg) at baseline, which did not significantly change after using FML, and were excluded from analysis. Of the 17 remaining patients, propensity score-matched analysis was conducted to compare them with 17 patients who did not receive FML, matching for the variables of age, gender, ethnicity, diagnosis, longest glaucoma medication duration, and surgery type. Patients with FML treatment had lower odds of requiring any post-operative intervention (including needling, surgery, or IOP-lowering medications) (OR 0.22, CI 0.049–0.95, p = 0.042) compared to patients who did not have pre-operative FML treatment. Conclusions: In patients with higher levels of MCP-1 pre-operatively, the use of FML for 2 weeks pre-operatively improved their early post-operative outcomes following trabeculectomy or phaco-trabeculectomy. Full article

Optineurin (OPTN) is a multifunctional adaptor protein that regulates diverse cellular processes, including inflammatory signaling, autophagy, vesicular trafficking, and immune responses. This multifaceted role of OPTN is made possible by the presence of a complex structure comprising multiple domains that interact with different proteins to exert various functions important for modulating key signaling processes. Mutations in OPTN are linked with several human pathologies including glaucoma, Paget’s disease of bone, Crohn’s disease, and neurodegenerative diseases such as amyotrophic lateral sclerosis, and dementia. Emerging evidence suggests that OPTN has a complex and context-dependent role in cancer biology as well. It is upregulated in pancreatic ductal adenocarcinoma and hepatocellular carcinoma but downregulated in lung and colorectal cancers, indicating its dual role as a potential oncogene or tumor suppressor depending on the cellular environment. Additionally, OPTN plays a critical role in preventing immune evasion in colorectal cancer by maintaining interferon-gamma receptor 1 (IFNGR1) expression and supporting dendritic cell-mediated T-cell priming, thereby enhancing antitumor immune responses. Despite its significance in oncogenic pathways and immune regulation, the therapeutic potential of targeting OPTN in cancer remains largely unexplored. This review aims to provide a comprehensive understanding of OPTN’s pleiotropic functions, highlighting its role in autophagy, inflammation, immune surveillance, and cancer progression. By elucidating its diverse regulatory mechanisms, we seek to encourage further research into the therapeutic implications of OPTN in cancer treatment and immunotherapy. Full article

Background/Objectives: To evaluate the long-term outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) in patients with glaucoma and to investigate if the usage of the prostaglandin analog latanoprost increases the risk of graft rejection. Methods: This study retrospectively reviewed 65 eyes of 61 patients with glaucoma who underwent DSAEK at King Abdulaziz University Hospital between 2009 and 2024. The risk factors for graft rejection were identified using Kaplan–Meier survival analysis and univariate and multivariate Cox regression models. Results: The graft survival rates among patients with glaucoma at 1, 3, and 5 years were 72.4%, 23.1%, and 11.5%, respectively. Latanoprost use was significantly associated with graft failure (71.4% vs. 28.6%, p = 0.024). The graft failure was mostly secondary failure (80%, p = 0.015) and was often linked to endothelial rejection episodes (62.5%). Other antiglaucoma medications were not associated with graft failure. Conclusions: Glaucoma decreases graft longevity after DSAEK. Latanoprost use may further increase the risk of graft rejection by enhancing inflammatory or immune responses. Prospective studies are warranted to confirm these findings. Full article

This study explored the use of physical methods, namely X-ray diffraction, atomic force microscopy, and energy-dispersive X-ray spectroscopy, to analyze the structure and composition of tear fluid desiccates. Tear samples were collected from patients with dry eye syndrome, glaucoma, and multiple sclerosis. Our results revealed significant differences in the crystallization patterns, chemical composition, and morphology of tear fluid among the disease groups compared to healthy individuals. XRD analysis identified variations in salt crystallization within tear fluid desiccates. AFM provided nanoscale morphological visualization. EDX determined the presence of key chemical elements. Our findings showed that changes in crystallization and unbalance of ionic composition in tear fluid may serve as potential markers for diagnosing ocular diseases. This study highlights the potential of these techniques for non-invasive diagnostics and contributes to the development of innovative strategies for monitoring structural properties in tear fluid desiccates of analyzed inflammatory, and neurodegenerative diseases. Full article