Journal
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume 49, Issue 3, Pages 1126-1135Publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.07-1234
Keywords
-
Categories
Funding
- NCRR NIH HHS [M01 RR000042, M01-RR00042] Funding Source: Medline
- NEI NIH HHS [R01 EY011115, R01 EY007042-22, R01 EY007042, P30-EY07003, EY02660, EY12298, EY11115, EY07042, P30 EY007003, R01 EY012298, R01 EY002660] Funding Source: Medline
Ask authors/readers for more resources
PURPOSE. To define rod and cone function further in terms of visual cycle mechanism, the retinal phenotype resulting from Rpe65 (retinoid isomerase I) deficiency in Nrl(-/-) mice having a single class of photoreceptors resembling wild-type cones was characterized and outcomes of retinoid supplementation evaluated. METHODS. Rpe65(-/-)/Nrl(-/-) mice were generated by breeding Rpe65(-/-) and Nrl(-/-) strains. Retinal histology, protein expression, retinoid content, and electroretinographic (ERG) responses were evaluated before and after treatment with 11-cis retinal by intraperitoneal injection. RESULTS Retinas of young Rpe65(-/-)/Nrl(-/-) mice exhibited normal lamination, but lacked intact photoreceptor outer segments at all ages examined. Rpe65, Nrl, and rhodopsin were not detected, and S-opsin and M/L-opsin levels were reduced. Retinyl esters were the only retinoids present. In contrast, Nrl(-/-) mice exhibited decreased levels of retinaldehydes and retinyl esters, and elevated levels of retinols. ERG responses were elicited from Rpe65(-/-)/Nrl(-/-) mice only at the two highest intensities over a 4-log-unit range. Significant retinal thinning and outer nuclear layer loss occurred in Rpe65(-/-)/Nrl(-/-) mice with aging. Administration of exogenous 11-cis retinal did not rescue retinal morphology or markedly improve ERG responses. CONCLUSIONS. The findings provide clarification of reported cone loss of function in Rpe65(-/-)/Nrl(-/-) mice, now showing that chromophore absence results in destabilized cone outer segments and rapid retinal degeneration. The data support the view that rod-dominant retinas do not have a cone-s pecific mechanism for 11-cis retinal synthesis and have potential significance for therapeutic strategies for rescue of cone-rich retinal regions affected by disease in the aging human population.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available