Article

Cone Degeneration Following Rod Ablation in a Reversible Model of Retinal Degeneration

Department of Ophthalmology, Center for Vision Research, SUNY Eye Institute, Upstate Medical University, Syracuse, NY 13210, USA.
Investigative ophthalmology & visual science (Impact Factor: 3.66). 01/2011; 52(1):364-73. DOI: 10.1167/iovs.10-5347
Source: PubMed

ABSTRACT Amphibian retinas regenerate after injury, making them ideal for studying the mechanisms of retinal regeneration, but this leaves their value as models of retinal degeneration in question. The authors asked whether the initial cellular changes after rod loss in the regenerative model Xenopus laevis mimic those observed in nonregenerative models. They also asked whether rod loss was reversible.
The authors generated transgenic X. laevis expressing the Escherichia coli enzyme nitroreductase (NTR) under the control of the rod-specific rhodopsin (XOP) promoter. NTR converts the antibiotic metronidazole (Mtz) into an interstrand DNA cross-linker. A visually mediated behavioral assay and immunohistochemistry were used to determine the effects of Mtz on the vision and retinas of XOPNTR F1 tadpoles.
NTR expression was detected only in the rods of XOPNTR tadpoles. Mtz treatment resulted in rapid vision loss and near complete ablation of rod photoreceptors by day 12. Müller glial cell hypertrophy and progressive cone degeneration followed rod cell ablation. When animals were allowed to recover, new rods were born and formed outer segments.
The initial secondary cellular changes detected in the rodless tadpole retina mimic those observed in other models of retinal degeneration. The rapid and synchronous rod loss in XOPNTR animals suggested this model may prove useful in the study of retinal degeneration. Moreover, the regenerative capacity of the Xenopus retina makes these animals a valuable tool for identifying the cellular and molecular mechanisms at work in lower vertebrates with the remarkable capacity of retinal regeneration.

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    • "In the mouse, expression of NTR driven by the control elements of the human CD2 locus has allowed to induce an extensive and specific T cell depletion in thymus and spleen (Drabek et al., 1997). More recently, transgenic expression of NTR has been successfully used in zebrafish and Xenopus to induce temporally controlled cell specific ablation of cardiomyocytes, pancreatic beta-cells, hepatocytes and rod photoreceptors (Curado et al., 2007; Pisharath et al., 2007; Curado et al., 2008; Choi et al., 2011). Here, we demonstrate that the same experimental strategy can be exploited to eliminate oligodendrocytes in a temporal-and spatial-specific manner in a transgenic Xenopus tadpole. "
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