Abstract
Abstract: :
Purpose: Mutations in the gene that encodes retinoschisin causes X–linked juvenile retinoschisis (XLRS), a degenerative disease of the retina. The XLRS retina displays macular atrophy, formation of cystic cavities within the retina, accumulation of extracellular filaments, and an abnormal b–wave of the electroretinogram. We have shown earlier that retinoschisin is secreted by photoreceptor cells, and then interacts with bipolar and Müller cells (Reid et al., 2003 J Neurosci 23: 6030–6040). These cell–cell interactions contribute to the development and maintenance of the cytoarchitectural and functional integrity of the retina. Therefore, regulation of retinoschisin's secretion is a critical stage for its function. It is known that retinoschisin mRNA is most abundant in the photoreceptor inner segments. We speculate that this is where retinoschisin is secreted by photoreceptor cells. Methods: Frozen sections of mouse retinas and dissociated retinal cells were double–labeled with a retinoschisin antibody and an antibody against either SNAP–25, syntaxin or VAMP. SNAP–25, syntaxin and VAMP are components of the exocytotic machinery, known as the SNARE complex. Colocalization of retinoschisin with these components of the SNARE complex were evaluated by fluorescent and confocal microscopy. Results: Our preliminary data showed that antibodies against SNAP–25, syntaxin and VAMP labeled the inner segments of photoreceptor cells. The SNAP–25 antibody labeled punctate structures along the cytoplasmic membrane of the inner segment of dissociated photoreceptor cells. These SNAP–25–positive puncta were also labeled by the anti–retinoschisin antibody.Conclusions:These results suggest that retinoschisin is probably secreted by exocytosis from the inner segments of photoreceptor cells.
Keywords: photoreceptors • proteins encoded by disease genes • cell-cell communication