ArticleInvestigative ophthalmology & visual science2011
Deletion of the p85alpha regulatory subunit of phosphoinositide 3-kinase in cone photoreceptor cells results in cone photoreceptor degeneration.
Article in Investigative ophthalmology & visual science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 49 citations in OpenAlex.
- Mechanism of Cone Degeneration in Retinitis Pigmentosa.Cellular and molecular neurobiology · 2023Review
- Ribosomal targeting strategy and nuclear labeling to analyze photoreceptor phosphoinositide signatures.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2022Article
- Insulin-like growth factor 1 receptor mediates photoreceptor neuroprotection.Cell death & disease · 2022Article
- Beyond Genetics: The Role of Metabolism in Photoreceptor Survival, Development and Repair.Frontiers in cell and developmental biology · 2022Review
- Mice deficient in UXT exhibit retinitis pigmentosa-like features via aberrant autophagy activation.Autophagy · 2021Article
- Regulation of Phosphoinositide Levels in the Retina by Protein Tyrosine Phosphatase 1B and Growth Factor Receptor-Bound Protein 14.Biomolecules · 2021Article
- Photoreceptor metabolic reprogramming: current understanding and therapeutic implications.Communications biology · 2021Review
- Diabetic Retinopathy and Insulin Insufficiency: Beta Cell Replacement as a Strategy to Prevent Blindness.Frontiers in endocrinology · 2021Article
- Insulin inhibits inflammation-induced cone death in retinal detachment.Journal of neuroinflammation · 2020Article
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- Endogenous insulin signaling in the RPE contributes to the maintenance of rod photoreceptor function in diabetes.Experimental eye research · 2019Article
- Therapeutic Benefits from Nanoparticles: The Potential Significance of Nanoscience in Retinal Degenerative Diseases.Journal of molecular biology & therapeutics · 2019Article
- Ribosomal protein S6 kinase 1 promotes the survival of photoreceptors in retinitis pigmentosa.Cell death & disease · 2018Article
- Pyruvate kinase M2 isoform deletion in cone photoreceptors results in age-related cone degeneration.Cell death & disease · 2018Article
- Metabolic and redox signaling in the retina.Cellular and molecular life sciences : CMLS · 2017Review
- The Warburg Effect Mediator Pyruvate Kinase M2 Expression and Regulation in the Retina.Scientific reports · 2016Article
- Activation of oncogenic tyrosine kinase signaling promotes insulin receptor-mediated cone photoreceptor survival.Oncotarget · 2016Article
- Phosphatidylinositol-3-phosphate is light-regulated and essential for survival in retinal rods.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeDownregulation of the retinal insulin/mTOR pathway in mouse models of retinitis pigmentosa is linked to cone cell death, which can be delayed by systemic administration of insulin. A classic survival kinase linking extracellular trophic/growth factors with intracellular antiapoptotic pathways is phosphoinositide 3-kinase (PI3K), which the authors have shown to protect rod photoreceptors from stress-induced cell death. The role of PI3K in cones was studied by conditional deletion of its p85α regulatory subunit.
methodsMice expressing Cre recombinase in cones were bred to mice with a floxed pi3k gene encoding the p85α regulatory subunit of the PI3K and were back-crossed to ultimately generate offspring with cone-specific p85α knockout (cKO). Cre expression and cone-specific localization were confirmed by Western blot analysis and immunohistochemistry (IHC), respectively. Cone structural integrity was determined by IHC using peanut agglutinin and an M-opsin-specific antibody. Electroretinography (ERG) was used to assess rod and cone photoreceptor function. Retinal structure was examined by light and electron microscopy.
resultsAn age-related cone degeneration was found in cKO mice, evidenced by a reduction in photopic ERG amplitudes and loss of cone cells. By 12 months of age, approximately 78% of cones had died, and progressive disorganization of synaptic ultrastructure was noted in surviving cone terminals in cKO retinas. Rod viability was unaffected in p85α cKO mice.
conclusionsThe present study suggests that PI3K signaling pathway is essential for cone survival in the mouse retina.
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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.