NEUROPROTECTIVE STRATEGIES IN GLAUCOMA: CURRENT EVIDENCE AND FUTURE DIRECTIONS

Аннотация

Glaucoma, a leading cause of irreversible blindness worldwide, is characterized by progressive optic nerve degeneration and loss of retinal ganglion cells. Traditional treatments focus mainly on lowering intraocular pressure (IOP), yet neurodegeneration often continues even with controlled IOP. This article reviews the emerging neuroprotective strategies in glaucoma management, emphasizing pharmacological agents, gene therapy, mitochondrial stabilization, and stem-cell-based approaches. Evidence suggests that neuroprotection targeting excitotoxicity, oxidative stress, inflammation, and impaired axonal transport can preserve retinal ganglion cell integrity and visual function. Current research also highlights the potential of neurotrophic factors, calcium channel blockers, and antioxidant compounds as adjuncts to conventional therapy. Although significant progress has been made, translating neuroprotective mechanisms into clinical application remains challenging. Future directions should focus on combination therapies integrating IOP control and neuronal preservation to halt disease progression and improve long-term outcomes in glaucoma patients. Keywords: Glaucoma, neuroprotection, retinal ganglion cells, oxidative stress, neurotrophic factors, apoptosis, intraocular pressure, mitochondrial dysfunction, optic nerve, visual preservation. Introduction Glaucoma represents a complex neurodegenerative optic neuropathy that results in irreversible visual loss due to damage to retinal ganglion cells (RGCs) and their axons. Elevated intraocular pressure remains the most important risk factor; however, glaucomatous damage can develop or progress despite adequate pressure control, suggesting that mechanisms beyond mechanical stress contribute to neurodegeneration. Pathophysiological processes include glutamate excitotoxicity, mitochondrial dysfunction, oxidative stress, neuroinflammation, and reduced neurotrophic support. These processes converge to induce apoptosis of RGCs and progressive visual field loss. The neuroprotective concept aims to directly target neuronal survival and prevent or delay irreversible optic nerve damage, thereby complementing traditional pressure-lowering therapies. Neuroprotective strategies include pharmacological interventions such as NMDA receptor antagonists, calcium channel blockers, and antioxidants, as well as novel modalities like gene therapy and stem cell transplantation. The goal is to sustain RGC function, preserve axonal integrity, and maintain visual performance. This paper reviews contemporary evidence for neuroprotective strategies in glaucoma and explores future prospects for integrating these approaches into comprehensive disease management. 94 Noyabr, 2025-Yil Materials and Methods A systematic review of recent studies from 2010 to 2024 was conducted using PubMed, Scopus, and Web of Science databases. Keywords used included “glaucoma,” “neuroprotection,” “retinal ganglion cell,” “oxidative stress,” and “neurotrophic factors.” Randomized controlled trials, meta-analyses, and experimental studies investigating neuroprotective mechanisms or therapeutic interventions were included. Exclusion criteria comprised studies without measurable neuroprotective outcomes, non-English publications, and reviews lacking primary data. Data extraction focused on neuroprotective mechanisms, therapeutic efficacy, safety profiles, and translational potential. Comparative analysis was performed to evaluate both established and emerging neuroprotective compounds in preclinical and clinical contexts. Parameters assessed included rate of RGC loss, optic nerve integrity, visual field progression, and patient-reported outcomes where available. Results The review included 52 studies comprising 22 clinical trials and 30 experimental models. Evidence indicated that lowering IOP alone slowed but did not fully prevent RGC degeneration. NMDA receptor antagonists such as memantine demonstrated significant neuroprotective effects in animal models, although human trials produced mixed results due to dosage and duration limitations. Calcium channel blockers, including nimodipine, improved ocular blood flow and RGC survival. Brimonidine, an α2-adrenergic agonist, exhibited both IOP- lowering and direct neuroprotective effects through modulation of apoptotic signaling and neurotrophic factor release. Antioxidant compounds like coenzyme Q10, Ginkgo biloba extract, and resveratrol reduced oxidative stress and preserved mitochondrial function. Gene therapy using vectors encoding brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) showed promise in restoring axonal transport and enhancing cell survival. Experimental stem cell therapies demonstrated the potential to replace damaged RGCs and promote endogenous regeneration through paracrine signaling. Overall, combination therapies targeting both IOP and neurodegeneration yielded superior outcomes in visual preservation compared to monothe