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(Investigative Ophthalmology and Visual Science. 2007;48:2799-2805.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-0922
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Genetic Ablation of Cone Photoreceptors Eliminates Retinal Folds in the Retinal Degeneration 7 (rd7) Mouse

Jichao Chen1 and Jeremy Nathans1,2,3,4

1From the Departments of Molecular Biology and Genetics, 2Neuroscience, and 3Ophthalmology, and the 4Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.

PURPOSE. Folds or pseudorosettes in the outer retina are commonly observed in animals with genetic, viral, or chemically induced retinal degeneration. This study examined the effect of genetic ablation of cone photoreceptors on the production of retinal folds in two mouse retinopathy models. One is the rd7/rd7 retina, a model of enhanced S-cone syndrome, Goldman-Favre syndrome, and clumped pigmentary retinopathy that is also associated with an approximately twofold excess of S-cones. The other is postnatal day (P)0 N-methyl-N-nitrosourea (MNU) treatment.

METHODS. A transgene that directs cone-specific expression of the diphtheria toxin A chain was used to ablate cone photoreceptors. Retinal folds, numbers of photoreceptors, and numbers of cones were quantified in retina flatmounts or transverse sections, and photoreceptor apoptosis was quantified by immunostaining for activated caspase 3.

RESULTS. Cone ablation by the cone-DTA transgene eliminated folds in the rd7/rd7 retina, whereas chemical ablation of up to 30% of rods (by exposure to MNU at P13) had little or no effect on folds in the rd7/rd7 retina. Cone ablation by the cone-DTA transgene had no effect on retinal folds produced by P0 MNU treatment or on the progressive loss of rod photoreceptors in the rd7/rd7 retina.

CONCLUSIONS. Despite their relatively low abundance, cones play a critical role in retinal folding in the rd7/rd7 retina. The relevant molecular and cellular mechanisms remain to be determined.






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Copyright © 2007 by the Association for Research in Vision and Ophthalmology