[Glial dysfunction-mediated pathogenesis of glaucoma].

Abstract

Glaucoma is the leading cause of blindness worldwide. Vision loss in glaucoma is caused by damage to retinal ganglion cells (RGCs), which are responsible for transmitting visual information from the retina to the brain. Glaucoma is a multifactorial disease with multiple risk factors, among which elevated intraocular pressure (IOP) is the most well-established. Currently, lowering IOP is the mainstay of glaucoma treatment. However, disease progression is frequently observed even in patients whose IOP is well controlled. Notably, the majority of Japanese glaucoma patients are diagnosed with normal-tension glaucoma (NTG). These observations highlight the urgent need to elucidate IOP-independent mechanisms contributing to glaucoma pathogenesis. In this context, increasing attention has been directed toward the potential role of glial cells in the development and progression of glaucoma. Glial cells are known to play critical roles in various neurodegenerative diseases. In glaucoma, glial activation and dysfunction have been documented in the ocular tissue of human patients, as well as in primate and rodent models. Importantly, glial activation is observed at early stages of glaucoma, even before detectable RGC loss occurs. This raises the possibility that glial dysfunction is not merely a secondary response to neuronal injury but may serve as a primary driver of disease onset. For example, deletion of glial cell-specific genes has been shown to induce NTG-like phenotypes. This article provides an overview of recent advances in our understanding of the role of glial cells in glaucoma pathogenesis, with a focus on insights gained from our own research.