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SN M Reid, C Yamashita, DB Farber; Interactions Of Photoreceptors With Bipolar And Müller Cells Via Retinoschisin . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2421.
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Purpose: Retinoschisin is a newly discovered protein. Mutations in the gene that encodes it are responsible for X-linked juvenile retinoschisis (XLRS). Retinoschisin and the XLRS pathology are both found in the inner and outer retina, whereas the protein production site, indicated by the mRNA localization, is only in the photoreceptors. There are two possibilities for this discrepancy. Since XLRS has an early onset, retinoschisin in the inner retina could be the remnant of the protein produced in this area during development. Alternatively, retinoschisin is produced in the outer retina and interacts with inner retinal cells such as Müller and bipolar cells after it is released from the photoreceptors. Here, we report the distribution of retinoschisin and its mRNA throughout postnatal development. We also examine the release of this protein from the retina and its interactions with different retinal cells. Methods: We used in situ hybridization and immunohistochemistry to examine the distribution of retinoschisin mRNA and of the translated protein, Western blot analyses and the culture of ocular tissues to study retinoschisin secretion, and the combination of permeabilization and immunocytochemistry to demonstrate the interactions of retinoschisin with retinal cells. Results: We show that the retina releases retinoschisin. Both the mRNA and protein are detectable within the first postnatal week and reach the adult pattern at the third postnatal week. Throughout development, retinoschisin is present in the outer and inner retina; whereas its mRNA is only seen in the outer retina. Both bipolar and Müller cells show retinoschisin staining on their surfaces. Retinoschisin is found inside Müller cells but not in bipolar cells. Conclusion: Retinoschisin is produced exclusively in the photoreceptor cells. After synthesis, retinoschisin is released into the extracellular space. Its presence within Müller cells supports our previous observation that retinoschisin may be taken up and transported by these cells to the inner retina. The presence of retinoschisin on the surface of bipolar and Müller cells reflects interactions, not described before, of the photoreceptors with these cells.
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