Factors of innate immunity in the pathogenesis of glaucoma and optic neuropathy

Balatskaya N.V., Petrov S.Yu., Kotelin V.I.

Helmholtz National Medical Research Center of Eye Diseases, Moscow, Russia

Primary open-angle glaucoma (POAG) is a multifactorial disease based on progressive optic neuropathy (ON) that leads to neurodegeneration of ganglion retinal cells and their axons, resulting in an initially irreversible loss of visual function. In addition to the main reasons for the onset and development of POAG - increased intraocular pressure, old age and genetic predisposition, the process of degenerative-destructive damage to the optic nerve is associated with a number of factors, among which the key role belongs to the pathological activation of immunological mechanisms deciphered due to advances in adaptive immunity research. The purpose of this review is to summarize the data of experimental and clinical studies devoted to the study of innate immunity and its regulation in the pathogenesis of ON. It has been shown that glial elements, being cells of the innate immune system in the retina, carry out recognition and form a response to damage patterns by regulating local inflammation in glaucoma. In the review the mechanisms of DAMPs involvement in the induction of local inflammation in POAG are discussed, of which the most studied to date are heat shock proteins, alarmin – HMGB1 (high-mobility group protein B1), as well as oxidatively modified biomolecules. Much attention is paid to TLRs, in particular, TLR4, which recognize hazard patterns, provide protection against damage under normal conditions and during the development of a pathological process in glaucoma. Interaction of TLRs with DAMPs triggers pro-inflammatory cell cascades, the production of cytokines, chemoattractant mediators that support inflammation in the nervous tissue. In addition to TLRs, the review discusses other groups of receptors, such as NLRs and RAGEs. The ways of activation and the sequence of assembly of the inflammasome complex (NLRP3) in the simulation of acute glaucoma in the experiment are described and a conceptual scheme for the activation of innate immunity in POAG is presented. Further research in the field of innate immunity will contribute to the full deciphering of the mechanisms of neuroinflammation, the development of biological markers for the diagnosis and monitoring of the pathological process, strategies for targeted therapy (approaches to the management of the local inflammatory response at the level of M1 and M2 transitions of microglia phenotypes, etc.) of glaucomatous optical neuropathy and neurodegenerative diseases of the retina.