Genetic ablation of cone photoreceptors eliminates retinal folds in the retinal degeneration 7 (rd7) mouse

Jichao Chen, Jeremy Nathans

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2799-2805
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume48
Issue number6
DOIs
StatePublished - Jun 2007

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Retinal Cone Photoreceptor Cells
Retinal Degeneration
Retina
Transgenes
Retinal Rod Photoreceptor Cells
Methylnitrosourea
Retinitis Pigmentosa
Caspase 3

ASJC Scopus subject areas

  • Ophthalmology

Cite this

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title = "Genetic ablation of cone photoreceptors eliminates retinal folds in the retinal degeneration 7 (rd7) mouse",
abstract = "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.",
author = "Jichao Chen and Jeremy Nathans",
year = "2007",
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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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