What is glaucoma?

Excerpt

Glaucoma, a leading cause of blindness in the world, can be challenging to diagnose because symptoms often appear at late stage of the disease, and challenging to treat because of the irreversible loss of retinal neurons. The term encompasses a heterogenous group of diseases that are characterized by altered biomechanics of anterior and posterior eye. These diseases tend to manifest as stiffening of the trabecular meshwork and increased production/reduced drainage of aqueous humor, together with retinal inflammation associated with activated microglia, Müller cells and astrocytes, and degeneration of retinal ganglion cells. In general, the phenotype is caused by a conjunction of risk factors such as age, family history, ethnic origin, high myopia, vascular disease and intraocular pressure (IOP). Current treatments are limited to lowering and stabilizing IOP, indicating that glaucoma is principally a disease of ocular mechanotransduction. Although the events that lead from IOP elevations to ganglion cell damage are not well defined, a body of recent work has pointed at mechanotransducing TRPV4, piezo and TREK-1 channels and immune mechanisms as key pressure targets in trabecular meshwork, ciliary body, retinal ganglion, endothelial cells and glia. Data indicate that dysfunctions of mechanotransduction mechanisms within the ganglion cell soma-dendrite, Müller cells and microglia may precede axonal degeneration, cupping of the optic nerve head and visual field damage which over the years have represented the golden standard of glaucoma diagnosis. Collectively, these recent studies predict the development of new therapies and diagnostic strategies to be contingent upon systematic delineation of molecular mechanisms that sense and transduce pressure in the eye. Thus, neuroprotection, a currently elusive goal, may be achieved via parallel suppression of pressure sensing in the anterior eye, retinal neurons, blood vessels and glia in order to achieve normalization of neuron-glia-blood vessel interactions, and the attendant reduction in immune activation.