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Yerina Ji, Eun-Jin Lee, Colleen Zhu, Norberto M. Grzywacz; Cellular Mechanisms Controlling the Mosaic of Surviving Cones in the S334ter-line-3-rat Model of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4993. doi: https://doi.org/.
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In the S334ter-line-3 rat (a transgenic model developed to express a rhodopsin mutation causing retinitis pigmentosa - RP), the rod’s death triggers a reorganization of the cone mosaic. Cones migrate into an orderly array of rings. This study was conducted to understand the cellular mechanisms controlling the resulting mosaic of surviving cones.
S334ter-line-3 rats were used as a model of RP with control animals being age-matched Sprague Dawley rats. All rats were kept under daily 12 h light/dark cycle. Intravitreal injections into the rats’ eyes were performed with either saline, AAA (disrupting Müller-cell processes), TIMP-1 (disrupting metalloproteinases), or with mixtures of AAA and TIMP-1. Three days after the injection, the rats were sacrificed and the retinas were tested for the organization of cones and Müller-cells by immunohistochemistry. Tests of cone survival were performed with Western-blot analysis.
We observed remodeling of Müller-cell processes in RP retinas; the processes were surrounding cones and filling the space inside their rings. In contrast, no ring of cones appeared in RP retinas collected from AAA-injected eyes. In turn, RP retinas from TIMP-1-injected eyes showed rings of clusters of cones, while TIMP-1 injection in normal eyes elicited formation of spatially random clusters of cones. Mixtures of AAA and TIMP-1 eliminated the rings of cones, causing salt-and-pepper distributions of these cells. Western-blot results showed reduction in the protein levels related to cones in the absence of rings but not otherwise.
At least two mechanisms may control the mosaic of surviving cones in S334ter-line-3 rats. Our results showed that Müller cells interact closely with cones, helping form ring mosaics in RP. Furthermore, the release of metalloproteinases from the retinal pigment epithelium may aid in the even spatial distribution of cones both normally and in rings. Ring formations may help to prolong the survival of cones.
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