Purchase this article with an account.
D. C. Lee, B. M. Tam, L. M. Hamm, O. L. Moritz; Partial Reversal o Retinal Degeneration in a P23H Mutant Rhodopsin Model of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4075.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The Xenopus laevis retina can regenerate after traumatic physical injury. We wanted to determine whether the X. laevis retina is also capable of regenerating photoreceptor cells after targeted cellular damage, specifically, rod photoreceptor degeneration in transgenic models of retinits pigmentosa.
We have previously developed and extensively characterized transgenic X. laevis inducible models of retinitis pigmentosa, including light-inducible P23H mutant rhodopsin and drug-inducible caspase 9 (iCasp9) models. In the current study, we induced acute rod photoreceptor degeneration in these models by light or drug exposure. We subsequently discontinued the degeneration-inducing stimuli, and monitored retinal regeneration by histology over an 8-week recovery period. All procedures were performed in accordance to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.
We found that retinal degeneration caused by P23H rhodopsin could be partially reversed, with regeneration of significant numbers of rod photoreceptors with normal morphology (including full-length rod outer segments) by the end of the 8-week recovery period. Conversely, retinal degeneration caused by iCasp9 was permanent. Using a rod-specific GFP marker, we were able to identify dystrophic rod photoreceptors lacking rod outer segments as the likely source of rod photoreceptor regeneration in the P23H retinas.
Light-induced P23H mutant rhodopsin-mediated degeneration is partially reversible. We identified that dystrophic but viable rod photoreceptors present after light-induced retinal degeneration are able to re-grow lost outer segments, and partially repopulate the retina, once the degeneration-inducing light stimulus is removed. However, rod photoreceptors that undergo drug-induced caspase-9 mediated apoptosis are permanently lost and do not regenerate. Thus, signals or pathways present in the X. laevis retina after traumatic injury that allow retinal regeneration via cell division or transdifferentiation of other cell types are absent in genetically inherited forms of retinal degeneration.
This PDF is available to Subscribers Only