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R. F. Mullins, E. I. Schindler, G. S. Enriquez, E. A. Faidley, M. H. Kuehn, E. M. Stone; Morphology and Gene Expression Analysis of ABCA4-associated Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4490.
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© ARVO (1962-2015); The Authors (2016-present)
Autosomal recessive retinitis pigmentosa (RP) is a rare hereditary form of retinal degeneration. In this report we sought to evaluate the morphological and gene expression changes that occur in advanced ARRP.
Eyes were obtained post-mortem from a patient with end-stage ARRP who was followed clinically for over 30 years. The coding sequences of rds, rhodopsin and ABCA4 genes were screened for disease causing mutations. Morphological changes in different regions of the retina were examined by routine histology and by immunohistochemistry with cell type specific markers directed against glia, neurons, and endothelial cells. A wedge of retinal/choroidal tissue was used for gene expression analysis using Affymetrix expression arrays. Gene expression and histological features were compared with those of unaffected control donors.
Genetic analysis of the RP eye identified 2 mutations in the ABCA4 gene IVS14+1G>C and Phe1440del1cT. Morphological evaluation revealed complete loss of the outer nuclear layer, remodeling of the inner retina, loss of retinal vasculature, and regional neovascularization. The RPE and choriocapillaris exhibited regional preservation. Microarray analysis revealed the expected loss of photoreceptor cell-associated transcripts, with preservation of a number of bipolar cell/ganglion cell mRNAs including those encoding the rod bipolar cell glutamate receptor (Grm6) and neurofilament heavy chains (NEFH). Glial fibrillary acidic protein was significantly increased at both the mRNA and protein levels.
The persistence of bipolar and ganglion cell transcripts suggests that, in spite of the significant plasticity that occurs during retinal degeneration, bipolar cells and ganglion cells remain at least partially differentiated. This study suggests that experimental therapies may have benefit even in advanced retinal degeneration.
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