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Cone-Enriched Cultures from the Retina of Chicken Embryos to Study Rod to Cone Cellular Interactions
Published on: March 20, 2021
Insulin receptor signaling in cones
Ammaji Rajala1, Radhika Dighe, Martin-Paul Agbaga
1Department of Ophthalmology, University of Oklahoma Health Sciences Center and Dean A McGee Eye Institute, Oklahoma City, Oklahoma 73104, USA.
The Journal of Biological Chemistry
|May 16, 2013
Summary
Cone cells, crucial for vision, degenerate in diseases like retinitis pigmentosa. This study reveals that phosphoinositide 3-kinase (PI3K) plays a vital role in cone survival, suggesting an endogenous neuroprotective pathway.
Area of Science:
- Ophthalmology
- Neuroscience
- Molecular Biology
Background:
- Age-related macular degeneration and diabetic retinopathy are leading causes of cone cell loss in humans.
- Cone cell death is a key feature in retinitis pigmentosa (RP), preceding rod cell death.
- Systemic insulin administration has shown promise in delaying cone death in RP mouse models lacking rods.
Purpose of the Study:
- To investigate the role of insulin receptor (IR) signaling and phosphoinositide 3-kinase (PI3K) in cone survival.
- To test the hypothesis that cones possess an endogenous PI3K-mediated neuroprotective pathway.
- To determine if rod-derived cone survival factors signal through cone PI3K.
Main Methods:
- Generated and analyzed p85α(-/-)/Nrl(-/-) double knock-out mice and rhodopsin mutant mice lacking p85α.
- Examined the effect of the p85α subunit of PI3K on cone survival in these models.
- Compared cone degeneration rates in mice with and without functional p85α.
Main Results:
- Conditional deletion of the p85α subunit of PI3K in cones led to age-related cone degeneration.
- Cone degeneration was significantly accelerated in double knock-out and rhodopsin mutant mice lacking p85α.
- These findings were observed even when healthy rods were present, suggesting an intrinsic cone pathway.
Conclusions:
- Cones appear to have an endogenous PI3K-mediated neuroprotective pathway essential for their survival.
- This intrinsic pathway is distinct from, but potentially complementary to, rod-derived cone survival signals.
- Targeting PI3K signaling in cones could offer a novel therapeutic strategy for retinal degenerative diseases.
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