ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
cGMP accumulation causes photoreceptor degeneration in CNG channel deficiency: evidence of cGMP cytotoxicity independently of enhanced CNG channel function.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 74 citations in OpenAlex.
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- Protein kinase G inhibition preserves photoreceptor viability and function in a new mouse model for autosomal dominant retinitis pigmentosa.Cell death & disease · 2025Article
- Clinical and Biochemical Characterization of Specific GUCY2D Alleles Associated With a Rare Form of Night Blindness.Investigative ophthalmology & visual science · 2025Article
- Inhibition of cGMP-Signalling Rescues Retinal Ganglion Cells From Axotomy-Induced Degeneration.Journal of neurochemistry · 2025Article
- Resveratrol Protects Photoreceptors in Mouse Models of Retinal Degeneration.Antioxidants (Basel, Switzerland) · 2025Article
- Loss of paired immunoglobin-like type 2 receptor B gene associated with age-related macular degeneration impairs photoreceptor function in mouse retina.Human molecular genetics · 2025Article
- Vulnerability of the NrlAdvances in experimental medicine and biology · 2025Article
- Promotion of endoplasmic reticulum retrotranslocation by overexpression of E3 ubiquitin-protein ligase synoviolin 1 reduces endoplasmic reticulum stress and preserves cone photoreceptors in cyclic nucleotide-gated channel deficiency.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- cGMP Signaling in Photoreceptor Degeneration.International journal of molecular sciences · 2023Review
- Review
- Multiomics analyses reveal early metabolic imbalance and mitochondrial stress in neonatal photoreceptors leading to cell death in Pde6brd1/rd1 mouse model of retinal degeneration.Human molecular genetics · 2022Article
- Effects of Storage Temperature on Indica-Japonica Hybrid Rice Metabolites, Analyzed Using Liquid Chromatography and Mass Spectrometry.International journal of molecular sciences · 2022Article
- Deficiency of thyroid hormone receptor protects retinal pigment epithelium and photoreceptors from cell death in a mouse model of age-related macular degeneration.Cell death & disease · 2022Article
- Kinase activity profiling identifies putative downstream targets of cGMP/PKG signaling in inherited retinal neurodegeneration.Cell death discovery · 2022Article
- Multilimbed membrane guanylate cyclase signaling system, evolutionary ladder.Frontiers in molecular neuroscience · 2022Review
- Achromatopsia: Genetics and Gene Therapy.Molecular diagnosis & therapy · 2022Review
- Review
- Regulation of retinal membrane guanylyl cyclase (RetGC) by negative calcium feedback and RD3 protein.Pflugers Archiv : European journal of physiology · 2021Review
- The role of cGMP-signalling and calcium-signalling in photoreceptor cell death: perspectives for therapy development.Pflugers Archiv : European journal of physiology · 2021Review
- Preservation of endoplasmic reticulum (ER) CaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Photoreceptor cyclic nucleotide-gated (CNG) channels regulate Ca(2+) influx in rod and cone photoreceptors. cGMP, the native ligand of the photoreceptor CNG channels, has been associated with cytotoxicity when its levels rise above normal due to defects in photoreceptor phosphodiesterase (PDE6) or regulation of retinal guanylyl cyclase (retGC). We found a massive accumulation of cGMP in CNGA3-deficient retina and investigated whether cGMP accumulation plays a role in cone degeneration in CNG channel deficiency. The time course study showed that the retinal cGMP level in Cnga3(-/-);Nrl(-/-) mice with CNGA3 deficiency on a cone-dominant background was sharply increased at postnatal day 8 (P8), peaked around P10-P15, remained high through P30-P60, and returned to near control level at P90. This elevation pattern correlated with photoreceptor apoptotic death, which peaked around P15-P20. In Cnga3(-/-);Gucy2e(-/-) mice lacking retGC1, cone density and expression levels of cone-specific proteins were significantly increased compared with Cnga3(-/-), consistent with a role of cGMP accumulation as the major contributor to cone death caused by CNG channel deficiency. The activity and expression levels of cGMP-dependent protein kinase G (PKG) were significantly increased in Cnga3(-/-);Nrl(-/-) retina compared with Nrl(-/-), suggesting an involvement of PKG regulation in cell death. Our results indicate that cGMP accumulation in photoreceptors can itself exert cytotoxic effect in cones, independently of CNG channel activity and Ca(2+) influx.
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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.