Abstract
Purpose: :
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 photoreceptor degeneration in a P23H mutant rhodopsin transgenic X. laevis model of retinits pigmentosa.
Methods: :
We have previously developed and extensively characterized a P23H mutant rhodopsin light-inducible model of retinitis pigmentosa. In the current study, acute rod photoreceptor degeneration was induced by light exposure and documented in sample animals by histology over a 2-week period. Contralateral eyes were also processed for computational molecular phenotyping (CMP) to assess their metabolic states. The degeneration-inducing stimuli was subsequently discontinued, and retinal changes were similarly monitored over a 2-week recovery period. All procedures were performed in accordance to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.
Results: :
Degenerating P23H photoreceptors persisted and did not immediately undergo apoptosis during the 2-week light damage period. Retinal degeneration caused by P23H rhodopsin and light damage could be partially reversed with regeneration of significant numbers of rod photoreceptors, likely from dystrophic rod photoreceptors lacking rod outer segments as the source of rod photoreceptor regeneration in the P23H retinas. Conversely, retinal degeneration caused by induction of apoptosis by direct activation of caspase 9 was permanent.
Conclusions: :
Light-induced retinal degeneration mediated by P23H mutant rhodopsin is partially reversible. In this model, many rod photoreceptors are dystrophic after light exposure, but remain viable. Destabilized P23H rhodopsin protein may induce an ER stress response as a cell protective mechanism. These degenerating photoreceptors are able to re-grow lost outer segments, and partially repopulate the retina, after the degeneration-inducing stimulus is removed. However, the X. laevis retina is not capable of regenerating photoreceptors that undergo apoptotic cell death.
Keywords: retinal degenerations: cell biology • photoreceptors • cell survival