ArticleHuman molecular genetics2017
Two pathways of rod photoreceptor cell death induced by elevated cGMP.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 54 citations in OpenAlex.
- Review of Therapeutic Potential of Coenzyme Q10 in Ophthalmology: Focus on Age-Related Macular Degeneration, Glaucoma, and Retinitis Pigmentosa.Antioxidants (Basel, Switzerland) · 2026Review
- Restoring Sight: The Journey of AIPL1 from Discovery to Therapy.International journal of molecular sciences · 2025Review
- Cyclic nucleotide signaling as a drug target in retinitis pigmentosa.FEBS letters · 2025Review
- dCasMINI-mediated therapy rescues photoreceptors degeneration in a mouse model of retinitis pigmentosa.Science advances · 2024Article
- Light regulation of rhodopsin distribution during outer segment renewal in murine rod photoreceptors.Current biology : CB · 2024Article
- Cone photoreceptor phosphodiesterase PDE6H inhibition regulates cancer cell growth and metabolism, replicating the dark retina response.Cancer & metabolism · 2024Article
- cGMP Signaling in Photoreceptor Degeneration.International journal of molecular sciences · 2023Review
- Effect on cell survival and cytoophidium assembly of the adRP-10-related IMPDH1 missense mutation Asp226Asn.Frontiers in cell and developmental biology · 2023Article
- Single-Cell Transcriptomic Profiling in Inherited Retinal Degeneration Reveals Distinct Metabolic Pathways in Rod and Cone Photoreceptors.International journal of molecular sciences · 2022Article
- cGMP Analogues with Opposing Actions on CNG Channels Selectively Modulate Rod or Cone Photoreceptor Function.Pharmaceutics · 2022Article
- 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
- Enhanced cGMP Interactor Rap Guanine Exchange Factor 4 (EPAC2) Expression and Activity in Degenerating Photoreceptors: A Neuroprotective Response?International journal of molecular sciences · 2022Article
- Programmed Non-Apoptotic Cell Death in Hereditary Retinal Degeneration: Crosstalk between cGMP-Dependent Pathways and PARthanatos?International journal of molecular sciences · 2021Review
- The role of cGMP-signalling and calcium-signalling in photoreceptor cell death: perspectives for therapy development.Pflugers Archiv : European journal of physiology · 2021Review
- Photoreceptor phosphodiesterase (PDE6): activation and inactivation mechanisms during visual transduction in rods and cones.Pflugers Archiv : European journal of physiology · 2021Review
- New In Vitro Cellular Model for Molecular Studies of Retinitis Pigmentosa.International journal of molecular sciences · 2021Article
- Visual Side Effects Linked to Sildenafil Consumption: An Update.Biomedicines · 2021Review
- Identification of Novel Substrates for cGMP Dependent Protein Kinase (PKG) through Kinase Activity Profiling to Understand Its Putative Role in Inherited Retinal Degeneration.International journal of molecular sciences · 2021Article
- RNA Biological Characteristics at the Peak of Cell Death in Different Hereditary Retinal Degeneration Mutants.Frontiers in genetics · 2021Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Cyclic-GMP is a second messenger in phototransduction, a G-protein signaling cascade that conveys photon absorption by rhodopsin to a change in current at the rod photoreceptor outer segment plasma membrane. Basal cGMP level is strictly controlled by the opposing actions of phosphodiesterase (PDE6) and retinal guanylyl cyclases (GCs), and mutations in genes that disrupt cGMP homeostasis leads to retinal degeneration in humans through mechanisms that are incompletely understood. The purpose of this study is to examine two distinct cellular targets of cGMP: the cGMP-gated (CNG) channels and protein kinase G (PRKG), and how each may contribute to rod cell death. Using a mouse genetic approach, we found that abolishing expression of CNG channels prolongs rod survival caused by elevated cGMP in a PDE6 mutant mouse model. This observation supports the use of channel blockers to delay rod death, which is expected to prolong useful vision through enhanced cone survival. However, the absence of CNG channel alone also caused abnormal cGMP accumulation. In a mouse model of CNG channel loss-of-function, abolishing PRKG1 expression had a long-lasting effect in promoting rod cell survival. Our data strongly implicate two distinct cGMP-mediated cell death pathways, and suggest that therapeutic designs targeting both pathways will be more effective at slowing photoreceptor cell death caused by elevated cGMP.
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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.