The role of plasticity in loss of vision caused by retinitis pigmentosa

NIH RePORTER · NIH · R01 · $463,927 · view on reporter.nih.gov ↗

Abstract

Abstract Retinitis pigmentosa (RP) is the most common group of inherited retinal disorders associated with progressive loss of vision. RP is typically diagnosed in adulthood following the onset of night blindness and impaired peripheral vision. Longitudinal studies of patients with RP reveal that their loss of visual acuity is significantly slower than the deterioration of their photoreceptor function. How the visual system sustains acuity despite the progressive loss of photoreceptors is unclear. Our hypothesis is that flexibility within the circuits of the visual system engage with the progressive loss of visual output to impair acuity. We will test our hypothesis by first characterizing the deficit in acuity and related functional characteristics in visual cortex and retina in using the rhodopsin P23H/+ (rho P23H/+) mutant mouse model. These mice have similar declines in retinal function and are a good model of human RP. Then we will evaluate whether enhancing or reducing experience-dependent plasticity affects the trajectory of the progressive loss of vision of rho P23H/+ mice by then characterizing the deficit in acuity and related functional characteristics in visual cortex and retina in using the rhodopsin P23H/+ (rho P23H/+) mutant mice that also lack a gene that limits plasticity in adult visual circuitry (nogo-66 receptor, ngr1) or that is required for visual plasticity (activity-regulated cytoskeleton-associated protein, ARC). Mice lacking ngr1 (ngr1 -/-) display greater visual plasticity than adult wild-type mice while mice lacking ARC (ARC -/-) exhibit reduced visual plasticity.

Key facts

NIH application ID
10826270
Project number
1R01EY035885-01
Recipient
UNIVERSITY OF LOUISVILLE
Principal Investigator
Maureen A McCall
Activity code
R01
Funding institute
NIH
Fiscal year
2024
Award amount
$463,927
Award type
1
Project period
2024-01-01 → 2024-07-31