Modern views on pathogenesis of glaucoma

Relevance Glaucoma is a multifactorial disease that is one of the leading causes of blindness worldwide. The modern understanding of glaucoma differs significantly from the previous understanding of it as the death of the retina due to increased intraocular pressure [1–3]. It is now considered a complex neurodegenerative process in which intraocular pressure is the only modifiable risk factor and the pathogenesis includes mechanical, vascular and metabolic aspects. New studies continue to expand our understanding of the pathogenesis of the disease. Glaucoma causes blindness due to the death of retinal ganglion cells (RGCs) due to increased intraocular pressure (IOP), which leads to disruption of the blood supply and axonoplasmic flow. The death of RGCs triggers a neurotoxic cascade with the release of glutamate, causing the death of neighboring cells, and the activation of astrocytes, which release inflammatory factors that damage RGCs and disrupt the blood-retinal barrier. In glaucoma, neuroinflammation caused by an imbalance of proinflammatory and antiinflammatory cytokines and the activation of glial cells plays an important role in retinal damage [4]. Inflammatory processes, oxidative stress and the release of cytokines form a vicious circle that aggravates neurodegeneration. Changes in the cytokine profile and growth factors in ocular tissues open up prospects for the use of biological therapy in the treatment of glaucoma. To date, it has been established that glaucoma is accompanied by changes in brain structures, which are actively studied. Data on the damage of various pathways (koniocellular, magnocellular and parvocellular) in the lateral geniculate bodies are contradictory. Interestingly, areas of the brain that are not related to the visual pathway, such as the hippocampus, frontoparietal cortex, and cerebellar cortex, are also affected. The RGCs require trophic factors (proteins) that are supplied to them by nearby retinal cells and from the brain via axonal transport. Increased IOP in the lamina cribrosa disrupts this transport, which may contribute to the development of glaucoma [5]. Conclusion The multifactorial nature of glaucoma requires further study of the complex mechanisms of its development. Understanding the role of intraocular pressure, vascular factors, neuroinflammation, and genetics is critical for the development of new effective treatments and preservation of vision. Keywords: glaucoma; retinal ganglion cells; neurodegeneration