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CJ Zeiss, E Johnson; Photoreceptor Apoptosis and Cell Cycle Re-entry Coincide in the rd mouse . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3663.
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Purpose: To determine whether apoptosis in photoreceptors of the rd mouse is accompanied by cell-cycle re-entry. Significance: Elevated expression of cell cycle proteins accompany neuronal death both in vitro and in naturally occurring neurodegenerative conditions. cdk2 inhibitors protect cells against apoptosis in vitro. Methods: Retinas from rd and age-matched control mice were compared at postnatal days (PN) 1, 7, 10, 12 and 15. They were examined for morphologic alterations, TUNEL staining, BrdU incorporation and expression of cell-cycle associated proteins. Results: Photoreceptor death proceeds in a central-to-peripheral gradient in rd retinas. Retinas from rd and wild-type mice are morphologically comparable until PN10. During PN 12-15, the width of the peripheral retina exceeds that of the central retina. The spatio-temporal patterns of DNA synthesis and photoreceptor death coincide in rd retinas. Both TUNEL and BrdU positive photoreceptor nuclei display a central-to-peripheral progression during PN10-15. Wild-type retinas had no TUNEL or BrdU positive photoreceptors after PN10. Cdk2, cdk4 and p27 proteins are detectable by immunohistomistry in rd, but not in wild-type retina. No difference in expression of cyclin E, p16 or p57 was noted. Conclusion: Development of rd and wild-type retinas appears comparable up to PN10. Thereafter, photoreceptor DNA synthesis, accompanied by expression of cell cycle proteins appears in the rd mouse, and is spatio-temporally correlated with photoreceptor death. This suggests that aberrent G1 progression of post-mitotic photoreceptors occurs in the rd mouse. The central-to-peripheral pattern of these changes reiterates the pattern of retinal development. Current work is focused on determining the relative contribution of cdk4/cyclin D, cdk2/cyclin A and cdk2/cyclin E complexes to G1 progression in rd retinas.
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