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P Hahn, T Lindsten, M Tolentino, J Bennett, AH Milam, C Thompson, J Dunaief; Bax and Bak are Essential for Developmental Apoptosis of Ocular Fetal Vasculature and INL Photoreceptors . Invest. Ophthalmol. Vis. Sci. 2002;43(13):829.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Normal developmental tissue remodeling often involves apoptotic regression of non-functional cells. We have recently demonstrated that bax and bak, two pro-apoptotic Bcl-2 members, mediate the regression of retinal neurons and ocular vessels during development (Hahn et al. ARVO 2001). Specifically, mice with targeted deletions in both bax and bak retain hyaloid vessels and extra inner retinal neurons. The aim of the current study is to determine the identity of these retained neurons and to further characterize the persistent vessels. Methods: Mice deficient in bax, bak, and bax/bak were generated along with their wild-type counterparts and adult eyes were analyzed by standard immunohistochemical and histologic techniques. Results: The retained neurons in the bax-/-bak-/- inner retina are comprised, in part, of rod photoreceptors ectopically situated in the outer INL. These ectopic rods are immunopositive for rod markers, including rod opsin, recoverin, and arrestin. Interestingly, we have identified subsets of these cells that are individually positive for certain rod markers, including cells that express rod opsin but not arrestin or recoverin and also cells that express arrestin but not rod opsin or recoverin. The persistent fetal vasculature, observed in bax-/-bak-/- mice as old as 8 months, includes all components of the hyaloid system: the hyaloid artery emerging from the optic nerve head, its intravitreal branches (vasa hyaloidea propria), and the perilenticular vascular network (tunica vasculosa lentis). Conclusions: These data implicate bax and bak as critical mediators of developmental regression of photoreceptors and fetal vessels, raising the issue of the primacy of cell-intrinsic versus cell-extrinsic mechanisms in developmental regression. These genes may play a role in pathological photoreceptor degenerations, including retinitis pigmentosa and AMD, as well as in eye diseases that involve persistent fetal structures, such as persistent fetal vasculature.
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