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S. W. Wang, E. Gonzalez, A. Moshiri, M. Wang, L. J. Frishman; Retinal Ganglion Cells Are Essential for Normal Retinogenesis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3733.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal ganglion cells (RGCs) are the first cell type to differentiate during retinal histogenesis. It has been postulated that specified RGCs subsequently influence the number and fate of the remaining progenitors to produce the rest of the retinal cell types. However, several genetic knockout models in mouse and zebrafish have argued against this developmental role for RGCs. Although it is known that RGCs secrete cellular factors implicated in cell proliferation, survival, and differentiation, until now, limited publications have shown that reductions in the RGC number cause significant changes in these processes. The purpose of this study is to examine the developmental outcomes in RGC-depleted retinas taking advantage of two knockout mouse lines.
A mouse line lack of two genes, math5 and brn3b, that are essential for RGC formation were created by crossing math5-/- and brn3b-/- lines. Immunostaining, TUNEL essay, and confocal microscopy were performed to analyze the retina at an early and a late stage during retinogenesis.
We showed that Math5 and Brn3b double null mice exhibited over a 99% reduction in the number of RGCs during early retinogenesis. This severe reduction of RGCs is accompanied by a drastic loss in the number of all other retinal cell types that was never seen before. Unlike Brn3b null or Math5 null animals, mice null for both alleles lack an optic nerve, have severe retinal dysfunction, and exhibit planar patterning defects.
Results of this study support the hypothesis that RGCs play a pivotal role in the late phase of mammalian retina development.
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