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P Fort, R Sarig, D Yaffe, U Nudel, J Sahel, A Rendon; Dystrophin Protein DP71 and Retina: a New Phenotype . Invest. Ophthalmol. Vis. Sci. 2002;43(13):661.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To clarify the importance of Dp71, one of the C-terminal short product of the Duchenne Muscular Dystrophy (DMD) gene expressed in the retina, we examined its cellular distribution and the perturbations induced by retinal ischemia in Dp71 knockout mice. Methods: Müller cell culture of wild and knockout mice strains has been done according to the protocol described by D Hicks and Y Courtois (Exp. Eye Res. 1990). The expression and cellular localization of dystrophins were determined by RT-PCR, Western-blot and immunocytochemistry method in cultured Müller cells. Retinal ischemia was performed on wild type and Dp71 knockout mice. Adult mice were anesthetized with intraperitoneal injections of pentobarbital (60 mg/kg). The anterior chamber pressure of the left eye was increased until 150 mm Hg for 60 min while the left eye served as non-ischemic control. The animals were sacrificed 15 days after reperfusion, and eyes were enucleated for histological and morphometric study. Results: We found that Dp71 was the only DMD gene product expressed by cultured Müller cells. We further characterized the Dp71 isoforms and found a differential subcellular localization as a function of the alternative splicing of the m RNA. Dp71 spliced for exon 78 was mainly localized in the cell nucleus, whereas the spliced one was found in the cytoplasm. Müller cells express another member of the dystrophin superfamilly: the utrophin. The evaluation of retinal injury after ischemia show that in KO-Dp71 mice the degenerative changes was more severe than those in wild type mice. Almost complete disappearance of the cells of the ganglion cell layer was observed in knockout mice. Conclusion: These data suggest that the absence of Dp71 in retina is the responsible of a retinal phenotype different than the already described in DMD patients and mdx3cv mutant mice (b-wave of the electroretinogram perturbed). Our results also indicate that Dp71 could play a neuroprotective role during ischemia.
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