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L. Menu dit Huart, O. Lorentz, T. Léveillard, J.A. Sahel; Regenerative Potential of the Adult Mouse Retina . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1684.
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Purpose: The retina grows throughout life in many fish and amphibian species. The ciliary marginal zone is a circumferential neurogenic zone located at the extreme peripheral retina. Recent results have demonstrated that a similar zone also exists in the chicken retina. Furthermore, it has been reported that cells with retinal stem cell properties could be isolated in vitro from the adult mouse and rat ciliary marginal zone. We investigated the in vivo neurogenic potential of the adult mouse retina. We tested the hypothesis that degeneration induces the neurogenic potential in the adult retina as observed in the cerebral cortex after induced injury. Methods: We used in vivo BrdU incorporation and immunohistochemisrty to study cell proliferation and differentiation in a "normal" and a "degenerating" retina (rd1). Results: We established that cells are able to incorporate BrdU in the extreme peripheral retina of both mice, with a number of BrdU positive cells nearly two times higher in the two-week old rd1 mouse compared to the wt, 3 hours after BrdU injection; 48 hours after BrdU injection, these cells express Pax6. This potential decreases with age (10, 14, 18, 28 days post-natal, 2-year old). In the photoreceptor cell layer of the two-week old degenerating retina only, DNA replication (BrdU incorporation, PCNA expression) occurs in cells expressing photoreceptor antigens (Rhodopsin, blue Opsin). This is consistent with either, a deregulation of cell cycle check points in apoptotic photoreceptors or, an induction of neurogenesis by degeneration; 73 %of BrdU labeled nuclei in the photoreceptor cell layer of the two-week old rd1 retina being tunel negative. Conclusions: Neurogenesis occurs in the peripheral retina of the adult mouse although it was thought to be restricted to inferior species in the so-called ciliary marginal zone. We now have to assess if the BrdU labeled photoreceptor nuclei of the two-week old rd1 retina are in an early phase of the apoptotic process or are newly formed photoreceptors.
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