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G.A. Pinzon–Duarte; Inner Retina Remodeling Precedes Photoreceptor Cell Loss in the rd Mouse . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1685.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:The molecular mechanisms producing photoreceptor cell death have been elucidated by the studies in rodent models of human retinal degeneration. The retinal degeneration (rd) mouse provides one of the best model for such studies, because photoreceptor loss is similar to that observed in humans with retinitis pigmentosa but with a more rapid time course; in the mouse photoreceptor loss is nearly complete by the third postnatal week. While considerable study has been made of the photoreceptor loss in these animals, little attention has been paid to the inner retina. Alternations in the inner retina, are likely to have an effect on the survival of photoreceptors and the timing of inner retinal cell loss has profound impact on therapeutic approaches designed to treat RD in humans. Methods: We compared the localization, onset and intensity of expression of several retinal proteins (calbindin, calretinin, GFAP, JH455, JH492, PKC, recoverin, and rhodopsin) in wild type (C57/BL6) and mutant (C3H/J6) animals from birth through the first 30 postnatal (P) days. Results: Until P10, the mutant and wild type retina underwent parallel histological differentiation attaining the same degree of lamination. Thereafter, the number of photoreceptor cells declined rapidly. The intensity of immunolabeling for calbindin– and PKC– was stronger at almost all stages examined in mutant retinas, even before photoreceptor cell loss started. The density of horizontal, and PKC+ bipolar cells remained constant, whereas the number of recoverin+ bipolar cells was increased. In contrast to most amarcrine markers which were constant, calretinin+ amacrine cells decreased in the rd mice. In mutant mice older than P10, an increase in the expression of glutamine synthetase was observed in Muller cells. In addition, GFAP was present in the same cells suggesting gliosis. Conclusions: Already prior to photoreceptor degeneration, alterations in the neuronal network of the inner retina were observed in rd mice. Thus, these early alterations have to be taken into account in the design and implementing rescue strategies in human degeneration.
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