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B.H. Weber, A. Gehrig, H. Schrewe; Investigation into the Final Pathway of Photoreceptor Degeneration in a Mouse Model of X-linked Juvenile Retinoschisis . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2836.
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Purpose: Deleterious mutations in RS1 encoding retinoschisin are associated with X-linked juvenile retinoschisis (RS), a common form of macular degeneration in males. Retinoschisin is a retina-specific polypeptide of 24 kDa that is secreted as a disulfide-linked oligomeric protein complex from both the rod and cone photoreceptors and the bipolar cells. The protein consists almost exclusively of a discoidin-like domain that has been implicated in cell adhesion and cell-cell interaction. To analyze the role of retinoschisin in the cellular pathology of RS, we have generated a knock-out mouse deficient in Rs1h, the murine ortholog of RS1. Here, we are interested to investigate whether, similar to other retinal degenerations, apoptosis may also be involved in photoreceptor cell degeneration in RS. Methods: Retinal cryosections from Rs1h-/Y and wildtyp mice of different postnatal stages were investigated for morphology and apoptotic events. Apoptotic cells were identified by TUNEL-staining (TdT-mediated X-dUTP nick end labeling) using the APO-BrdU-Kit (Phoenix Flow Systems). Results: Our results indicate that regular apoptosis occurs during early differentation of Rs1h-/Yand wild type retinae in all retinal layers investigated (outer and inner nuclear layers and ganglion cell layer). However, in contrast to wildtype retinae, the number of TUNEL-stained photoreceptor nuclei increases dramatically between postnatal day 14 and 21 in Rs1h-/Y mice. By day 21 p.n. virtually all rod photoreceptors are degraded via apoptotic cell death. Conclusions: Our data show that apoptosis is the final pathway of potoreceptor cell death in the Rs1h-/Y mouse although the rate of degeneration appears markedly slower compared to other retinal degeneration mouse models.
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