Retinal Degeneration, Remodeling and Plasticity

Excerpt

Retinal degeneration and remodeling encompasses a group of pathologies at the molecular, cellular and tissue levels that are initiated by inherited retinal diseases like retinitis pigmentosa (RP), genetic and environmental diseases like age-related macular degeneration (AMD) and other insults to the eye/retina including trauma and retinal detachment. These retinal changes and apparent plasticity result in neuronal rewiring and reprogramming events that include alterations in gene expression, de novo neuritogenesis as well as formation of novel synapses, creating corruptive circuitry in bipolar cells through alterations in the dendritic tree and supernumerary axonal growth. In addition, neuronal migration occurs throughout the vertical axis of the retina along Müller cell columns showing altered metabolic signals, and retinal pigment epithelium (RPE) invades the retina forming the pigmented bone spicules that have been classic clinical observations of RP diseases.

Retinal photoreceptors drive signal processing networks in the neural retina comprising bipolar, horizontal, amacrine and ganglion cells. It has been historically thought that retinal degenerative diseases such as RP affect the sensory retina, leaving the neural retina relatively unscathed. This is incorrect as the resulting loss of rod and cone input to the neural retina constitutes deafferentation and remodeling at the cellular and molecular level becomes unavoidable (1-22) .

Retinal degenerative diseases have a number of potential initiating events that result from naturally occurring disease processes (23), trauma like retinal detachment (24, 25) or any of the forms of retinitis pigmentosa (5, 23, 26, 27), but regardless of cause, if photoreceptors are lost, particularly cones, a sequence of progressive events is initiated that induces negative plastic remodeling of the neural retina (9-11, 14, 15, 21, 22, 28, 29). Essentially every disease process that results in photoreceptor loss triggers retinal remodeling as the final common pathway culminating with cell death and topological restructuring of the retina. The progression of retinal remodeling is like the negative plasticity that occurs in CNS pathologies like trauma and epilepsy and constitutes substantial impediments to rescue strategies of all types.