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Orson L. Moritz, Damian C. Lee, Lisa M. Hamm; Comparison Of The Regenerative Responses In The Xenopus Laevis Retina After Targeted Ablation Of Rod Photoreceptors Versus Surgical Removal Of Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4344.
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© ARVO (1962-2015); The Authors (2016-present)
The Xenopus laevis retina can regenerate after traumatic physical injury. We wanted to further characterize this regenerative capacity, and also determine whether the X. laevis retina is also capable of regenerating photoreceptor cells lost through apoptotic cell death in an inducible transgenic X. laevis model of retinits pigmentosa.
We previously developed and characterized a transgenic drug-inducible caspase 9 (iCasp9) X. laevis model of retinitis pigmentosa. In the current study, we induced acute rod photoreceptor apoptosis in this X. laevis model by drug exposure. We subsequently monitored the ability of X. laevis to regenerate lost photoreceptors either on its own, by simulating physical injury or by ectopic supplementation of basic fibroblast growth factor (bFGF). All procedures were performed in accordance to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.
Direct activation of caspase 9 in rod photoreceptors resulted the initiation of apoptosis and complete removal of rod photoreceptors by 4 days, as evidenced by apoptotic morphologies, TUNEL assay, and lack of GFP fluorescence. Photoreceptors lost by apoptosis were not replaced over a 8-week recovery timeframe. Physical disruption of rod-ablated retina was repaired by the end of a 3-week timeframe but did not result in rod photoreceptor regeneration. Furthermore, ectopic supplementation of bFGF did not stimulate regeneration of photoreceptors lost by apoptosis. However, bFGF supplementation increased the rate of regeneration of retina (including rod photoreceptors) in eyes from which retinal tissue was surgically removed.
Rod photoreceptors that undergo drug-induced caspase-9 mediated apoptosis are permanently lost and do not regenerate. The X. laevis neural retina (including photoreceptors), can regenerate in retinectomized eyes, and this regeneration is promoted by supplementation with bFGF. However, bFGF does not promote regeneration of rod photoreceptors that are lost by targeted apoptosis. It is interesting that the X. laevis retina possesses the capacity to regenerate only in response to certain types of injury; further investigation of the signals that promote regeneration in these animals may be relevant to the development of treatments for RP.
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