Abstract
Abstract: :
Purpose: Autosomal dominant optic atrophy (DOA) is the most commonly inherited optic neuropathy, and is manifest as a primary degeneration of retinal ganglion cells (RGCs). The gene responsible for DOA, designated Optic Atrophy Type 1 (OPA1), has recently been cloned and mapped to human chromosome 3q28. OPA1 is a component of the mitochondrial fusion/fission machinery and belongs to a family of highly conserved Dynamin–related GTPases. Although OPA1 expression has recently been reported in neural retina and optic nerve, the distribution pattern of OPA1 is still controversial. We have determined the cellular localization and expression of OPA1in the normal rodent retina and optic nerve. Methods: By using specific antibodies, we performed immunohistochemistry on paraffin sections and immunoblot analyses on homogenates of rat retina and optic nerve. To identify the cell type expressing OPA1 in the retinal ganglion cell layer (GCL), RGCs were retrogradely labeled with Fluoro–Gold. Immunocytochemistry was also performed on cultured RGCs. Results: In the normal rat retina, OPA1 immunoreactivity was observed in the outer plexiform layer. Additionally, OPA1 immunoreactivity was present in the GCL as well as the inner plexiform layer. In the GCL, OPA1 immunoreactivity was detected in RGCs. In cultured RGCs, OPA1 immunoreactivity was most intense in the mitochondria of the processes and cell bodies. In the normal rat optic nerve, OPA1 immunoreactivity was present in axonal mitochondria. However, OPA1 immunoreactivity was not observed in astrocytes and oligodendrocytes of the normal rat optic nerve. Conclusion: These results suggest that OPA1 is predominantly expressed in the RGCs of the normal rat retina as well as in the axons of the normal rat optic nerve. This may explain the vulnerability of retinal ganglion cells to degeneration by OPA–1 loss of function. Supported by R01 EY05477, R01 NS047456
Keywords: retina: proximal (bipolar, amacrine, and ganglion cells) • optic disc • immunohistochemistry