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OPA1, the disease gene for autosomal dominant optic atrophy, is specifically expressed in ganglion cells and intrinsic neurons of the retina

Item Type:Article
Title:OPA1, the disease gene for autosomal dominant optic atrophy, is specifically expressed in ganglion cells and intrinsic neurons of the retina
Creators Name:Pesch, U.E.A. and Fries, J.E. and Bette, S. and Kalbacher, H. and Wissinger, B. and Alexander, C. and Kohler, K.
Abstract:PURPOSE. Autosomal dominant optic atrophy is a hereditary disorder characterized by progressive loss of vision and caused by mutations in a dynamin-related gene, OPA1, which translates into a protein with a mitochondrial leader sequence. In this study the OPA1 gene and its protein were localized in the rat and mouse retina, and its rat orthologue, rOpa1, was identified. METHODS. The rOpa1 cDNA was isolated by using reverse transcribed cDNA from total RNA obtained from a rat retinal ganglion cell line. The spatial and temporal expression patterns of OPA1 and its gene product were investigated by RNA in situ hybridization and immunohistochemistry in mouse and rat retinas. To characterize further the OPA1-positive neurons, retinal ganglion cells were retrogradely labeled by an immunogold fluorescent tracer or double labeled with OPA1 and choline acetyltransferase or calbindin antibodies. RESULTS. Protein sequence alignment revealed a 96% identity between rat and human OPA1 mRNA. OPA1 expression was found as early as postnatal day 3 in the developing rodent retina. In the mature retina, the OPA1 gene and its protein were found not only in retinal ganglion cells, but also in starburst amacrine cells and horizontal cells, both of which are involved in lateral signal processing within the retina. However, OPA1 was absent from mitochondria rich nerve fibers and photoreceptor indicating a specific role for OPA1 in signal processing rather than in the requirement of mitochondrial energy supply in the retina. CONCLUSIONS. The data suggest an important and specific function of the OPA1 protein, not only in the optic nerve forming ganglion cells but also in the intrinsic signal processing of the inner retina.
Keywords:Autosomal Dominant Optic Atrophy, Developmental Gene Expression Regulation, GTP Phosphohydrolases, Immunohistochemistry, Inbred C57BL Mice, In Situ Hybridization, Messenger RNA, Molecular Cloning, Neurons, Retina, Retinal Ganglion Cells, Western Blotting, Animals, Mice, Rabbits, Rats
Source:Investigative Ophthalmology & Visual Science
Publisher:Association for Research in Vision and Ophthalmology
Page Range:4217-4225
Date:1 January 2004
Official Publication:https://doi.org/10.1167/iovs.03-1261
PubMed:View item in PubMed

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