M. Dubois-dauphin et al., Early postnatal Muller cell death leads to retinal but not optic nerve degeneration in NSE-HU-BCL-2 transgenic mice, NEUROSCIENC, 95(1), 2000, pp. 9-21
Topographically localized over-expression of the human Bcl-2 protein in ret
inal glial Muller cells of a transgenic mice (line 71) leads to early postn
atal apoptotic Muller cell death and retinal degeneration. Morphological, i
mmunohistological and confocal laser microscopic examination of transgenic
and wild-type retinas were achieved on paraffin retinal sections, postnatal
ly. Apoptosis occurs two to three days earlier in the internal nuclear laye
r of transgenic retinae, than in wild-type littermates. In parallel there w
as a progressive disappearance of transgenic Hu-Bcl-2 over-expression, as w
ell as of the Muller cell markers, cellular retinaldehyde-binding protein a
nd glutamine synthetase. This phenomenon lad to retinal dysplasia, photorec
eptor apoptosis end then retinal degeneration and proliferation ore retinal
pigment epithelium. The optic nerve, however, remains intact. Two compleme
ntary observations confirm the pro-apoptotic action of Bcl-2 over-expressio
n in Muller cells: (i) in the peri-papillary and peripheral regions where t
he 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 i
nspite of total retinal degeneration elsewhere.
We conclude that retinal dysplasia and degeneration are linked to primary M
uller cell disruption. Besides its generally accepted anti-apoptotic functi
on, over-expression of Bcl-2 also exerts a pro-apoptotic action, at least i
n immature Muller glia. One may suppose that Bcl-2 translocation resulting
in its over-expression in retinal Muller cells could be a putative mechanis
m for early retinal degeneration. (C) 1999 IBRO. Published by Elsevier Scie
nce Ltd.