Retinal remodeling in human retinitis pigmentosa. (September 2016)

• Record Type: Journal Article
• Authors: Jones, B.W.; Pfeiffer, R.L.; Ferrell, W.D.; Watt, C.B.; Marmor, M.; Marc, R.E.
• Is Part Of: Experimental eye research. Volume 150(2016:Sep.)
• Page Start: 149
• Page End: 165
• Publication Date: 2016-09
• Subjects: Retinitis pigmentosa (RP) -- Retinal pigment epithelium (RPE) -- Computational molecular phenotyping (CMP) -- Retina -- Cone photoreceptor -- Rod photoreceptor -- Amacrine cell -- Bipolar cell -- Ganglion cell -- Müller cell -- Retinal remodeling -- Neural remodeling; RP retinitis pigmentosa -- RPE retinal pigment epithelium -- GS glutamine synthetase -- GABA γ-aminobutyric acid -- CRALBP cellular retinaldehyde binding protein 1 -- EM electron microscopy -- RGB red green blue -- ONL outer nuclear layer -- ISODATA Iterative Self-Organizing Data Analysis Technique -- CMP Computational Molecular Phenotyping; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2016.03.018
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt the function or architecture of the photoreceptors. While RP can initially be a disease of photoreceptors, there is increasing evidence that the inner retina becomes progressively disorganized as the outer retina degenerates. These alterations have been extensively described in animal models, but remodeling in humans has not been as well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding of the retinal remodeling process in humans. We describe cone mediated preservation of overall topology, retinal reprogramming in the earliest stages of the disease in retinal bipolar cells, and alterations in both small molecule and protein signatures of neurons and glia. Furthermore, while Müller glia appear to be some of the last cells left in the degenerate retina, they are also one of the first cell classes in the neural retina to respond to stress which may reveal mechanisms related to remodeling and cell death in other retinal cell classes. Also fundamentally important is the finding that retinal network topologies are altered. Our results suggest interventions that presume substantial preservation of the neural retina will likely fail in late stages of the disease. Even early intervention offers no guarantee that the interventions will be immune to progressive remodeling. Fundamental work in the biology and mechanisms of disease progression are needed to support vision rescue strategies. Highlights: Demonstrate advanced negative plasticity and remodeling in human retinitis pigmentosa (RP) prior to photoreceptor loss. Alterations in both small molecule and protein signatures of neurons and glia. Müller cells are the first cells to show metabolic stress in retina and the last cells left in degenerate retina. Retinal network topologies are altered in RP. Unless we understand the mechanisms of retinal degeneration, interventions designed to rescue vision loss will likely fail.