| First Author | Dubois-Dauphin M | Year | 2000 |
| Journal | Neuroscience | Volume | 95 |
| Issue | 1 | Pages | 9-21 |
| PubMed ID | 10619458 | Mgi Jnum | J:60078 |
| Mgi Id | MGI:1352600 | Doi | 10.1016/s0306-4522(99)00313-9 |
| Citation | Dubois-Dauphin M, et al. (2000) Early postnatal Muller cell death leads to retinal but not optic nerve degeneration in NSE-Hu-Bcl-2 transgenic mice. Neuroscience 95(1):9-21 |
| abstractText | Topographically localized over-expression of the human Bcl-2 protein in retinal glial Muller cells of a transgenic mice (line 71) leads to early postnatal apoptotic Muller cell death and retinal degeneration. Morphological, immunohistological and confocal laser microscopic examination of transgenic and wild-type retinas were achieved on paraffin retinal sections, postnatally. Apoptosis occurs two to three days earlier in the internal nuclear layer of transgenic retinae, than in wild-type littermates. In parallel there was a progressive disappearance of transgenic Hu-Bcl-2 over-expression, as well as of the Muller cell markers, cellular retinaldehyde-binding protein and glutamine synthetase. This phenomenon led to retinal dysplasia, photoreceptor apoptosis and then retinal degeneration and proliferation of the retinal pigment epithelium. The optic nerve, however, remains intact. Two complementary observations confirm the pro-apoptotic action of Bcl-2 over-expression in Muller cells: (i) in the peri-papillary and peripheral regions where the transgene Bcl-2 is not expressed, cellular retinaldehyde-binding protein or glutamine synthetase immunostaining persist and Muller glia do not die; and (ii) the retina conserves a normal organisation in these two regions in spite of total retinal degeneration elsewhere. We conclude that retinal dysplasia and degeneration are linked to primary Muller cell disruption. Besides its generally accepted anti-apoptotic function, over-expression of Bcl-2 also exerts a pro-apoptotic action, at least in immature Muller glia. One may suppose that Bcl-2 translocation resulting in its over-expression in retinal Muller cells could be a putative mechanism for early retinal degeneration. |
