The role of neuroinflammation in glaucoma

Abstract

Glaucoma is a chronic neurodegenerative disorder characterized by progressive damage and loss of retinal ganglion cells (RGCs). It is considered one of the leading causes of irreversible blindness in the older population. There are estimates that glaucoma will affect 80 million individuals worldwide by the end of this decade, and yet we are still not able to identify the signals and the mechanisms that trigger this neurodegenerative disease. Various hypotheses have been generated to address the causes of the progressive RGC death that characterizes the disease. Age and increased intraocular pressure (IOP) have been established as the main risk factors for the development of glaucoma. Recent studies have identified additional factors that play a role in the pathogenesis of this complex multifactorial disease, including inflammation, oxidative stress, vascular dysregulation, disrupted axonal transport of neurotrophic factors, and the release of neurotoxic agents such as glutamate, nitric oxide and free radicals. The currently approved therapies for glaucoma that seek to reduce IOP, including medications, laser treatment, and surgery, are unable to reliably stop RGC loss and functional impairment. Considering the significant personal, medical and socio-economic impacts of glaucoma as a leading cause of blindness, there is a pressing need for new innovative treatment strategies. Here we focus on the role of neuroinflammation in glaucoma and the opportunities that new findings in this area have for the development of future therapeutics.

Keywords

glaucoma / neuroinflammation / immune system / complement / Toll-likereceptors / IL-1 / TNFα / blood retinal barrier / metalloproteinases