ArticleHuman molecular genetics2015
Genetic deletion of S-opsin prevents rapid cone degeneration in a mouse model of Leber congenital amaurosis.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Gene therapy for age-related macular degeneration: a promising frontier in vision preservation.Cell communication and signaling : CCS · 2025Review
- Effects of Different Spectrum of LEDs on Retinal Degeneration Through Regulating Endoplasmic Reticulum Stress.Translational vision science & technology · 2023Article
- Retinoid therapy restores eye-specific cortical responses in adult mice with retinal degeneration.Current biology : CB · 2022Article
- Visual pigment-deficient cones survive and mediate visual signaling despite the lack of outer segments.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Deletion of M-Opsin Prevents M Cone Degeneration in a Mouse Model of Leber Congenital Amaurosis.The American journal of pathology · 2020Article
- Novel molecular mechanisms for Prph2-associated pattern dystrophy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Endoplasmic reticulum (ER) CaThe Journal of biological chemistry · 2017Article
- Advances in Gene Therapy for Diseases of the Eye.Human gene therapy · 2016Review
- Lecithin:Retinol Acyltransferase: A Key Enzyme Involved in the Retinoid (visual) Cycle.Biochemistry · 2016Review
- Advances in understanding the molecular basis of the first steps in color vision.Progress in retinal and eye research · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in RPE65 or lecithin-retinol acyltransferase (LRAT) disrupt 11-cis-retinal synthesis and cause Leber congenital amaurosis (LCA), a severe hereditary blindness occurring in early childhood. The pathology is attributed to a combination of 11-cis-retinal deficiency and photoreceptor degeneration. The mistrafficking of cone membrane-associated proteins including cone opsins (M- and S-opsins), cone transducin (Gαt2), G-protein-coupled receptor kinase 1 (GRK1) and guanylate cyclase 1 (GC1) has been suggested to play a role in cone degeneration. However, their precise role in cone degeneration is unclear. Here we investigated the role of S-opsin (Opn1sw) in cone degeneration in Lrat(-) (/-), a murine model for LCA, by genetic ablation of S-opsin. We show that deletion of just one allele of S-opsin from Lrat(-) (/-) mice is sufficient to prevent the rapid cone degeneration for at least 1 month. Deletion of both alleles of S-opsin prevents cone degeneration for an extended period (at least 12 months). This genetic prevention is accompanied by a reduction of endoplasmic reticulum (ER) stress in Lrat(-) (/-) photoreceptors. Despite cone survival in Opn1sw(-/-)Lrat(-) (/-) mice, cone membrane-associated proteins (e.g. Gαt2, GRK1 and GC1) continue to have trafficking problems. Our results suggest that cone opsins are the 'culprit' linking 11-cis-retinal deficiency to cone degeneration in LCA. This result has important implications for the current gene therapy strategy that emphasizes the need for a combinatorial therapy to both improve vision and slow photoreceptor degeneration.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.