| First Author | Ivanovic I | Year | 2011 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 52 |
| Issue | 6 | Pages | 3775-83 |
| PubMed ID | 21398281 | Mgi Jnum | J:232389 |
| Mgi Id | MGI:5776685 | Doi | 10.1167/iovs.10-7139 |
| Citation | Ivanovic I, et al. (2011) Deletion of the p85alpha regulatory subunit of phosphoinositide 3-kinase in cone photoreceptor cells results in cone photoreceptor degeneration. Invest Ophthalmol Vis Sci 52(6):3775-83 |
| abstractText | PURPOSE: Downregulation 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 p85alpha regulatory subunit. METHODS: Mice expressing Cre recombinase in cones were bred to mice with a floxed pi3k gene encoding the p85alpha regulatory subunit of the PI3K and were back-crossed to ultimately generate offspring with cone-specific p85alpha 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. RESULTS: An 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 p85alpha cKO mice. CONCLUSIONS: The present study suggests that PI3K signaling pathway is essential for cone survival in the mouse retina. |
