Persistent remodeling and neurodegeneration in late-stage retinal degeneration

Publication date: Available online 26 July 2019Source: Progress in Retinal and Eye ResearchAuthor(s): Rebecca L. Pfeiffer, Bryan William Jones, Robert E. MarcAbstractRetinal remodeling is a progressive series of negative plasticity revisions that arise from retinal degeneration, and are seen in retinitis pigmentosa, age-related macular degeneration and other forms of retinal disease. These processes occur regardless of the precipitating event leading to degeneration. Retinal remodeling then culminates in a late-stage neurodegeneration that is indistinguishable from progressive central nervous system (CNS) proteinopathies. Following long-term deafferentation from photoreceptor cell death in humans, and long-lived animal models of retinal degeneration, most retinal neurons reprogram, then die. Glial cells reprogram into multiple anomalous metabolic phenotypes. At the same time, survivor neurons display degenerative inclusions that appear identical to progressive CNS neurodegenerative disease, and contain aberrant α-synuclein (α-syn) and phosphorylated α-syn. In addition, ultrastructural analysis indicates a novel potential mechanism for misfolded protein transfer that may explain how proteinopathies spread. While neurodegeneration poses a barrier to prospective retinal interventions that target primary photoreceptor loss, understanding the progression and time-course of retinal remodeling will be essential for the establishment of windows of therapeutic intervention and appr...

Source: Progress in Retinal and Eye Research - July 26, 2019 Category: Opthalmology Source Type: research