TY - JOUR
T1 - Genetic ablation of cone photoreceptors eliminates retinal folds in the retinal degeneration 7 (rd7) mouse
AU - Chen, Jichao
AU - Nathans, Jeremy
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2007/6
Y1 - 2007/6
N2 - 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)O 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 PO 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.
AB - 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)O 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 PO 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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U2 - 10.1167/iovs.06-0922
DO - 10.1167/iovs.06-0922
M3 - Article
C2 - 17525215
AN - SCOPUS:34347251964
SN - 0146-0404
VL - 48
SP - 2799
EP - 2805
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 6
ER -