The long-term objective of this research is to find a cure for retinal degenerative diseases such as RP. The """"""""first generation"""""""" models, mutant rhodopsin transgenic mice, have yielded important results: (1) identification of apoptosis as the final common pathway of photoreceptor death in rodent models of RP and (2) discovery of non-autonomy of mutant gene action in chimeras. These results indicate that mechanisms other than those immediately caused by the RP-inducing mutations may play key roles in the phenotypic manifestation of human RP. With an RP-inducing mutation in human rhodopsin, for example, the gene in question is expressed only in rod photoreceptors, yet the cone photoreceptors somehow die as well. During the early stages of RP, some cones die, along with most of the rods; nevertheless, a large population of cones survive, but then degenerate slowly, over decades. Saving these cones, which survive long after most of the rods have disappeared, is one of the critical issues for RP therapeutic research. The pig's eye is anatomically human-like, and unlike rodents, its retina is well-endowed with cones. The applicant's newly-developed """"""""second generation"""""""" model of RP, transgenic pigs expressing the rhodopsin Pro347Leu mutation, undergo retinal degeneration. By two months postnatal, most of the rods and some cones have died. Nevertheless, a large population of cones survive, but then degenerate slowly; residual cones that are grossly abnormal have been identified at 20 months of age. Between two and six months of age, however, the surviving cones appear, morphologically, close to normal. Any treatment that can prolong the survival of these cones, therefore, will become a potential therapy for human RP. Hence, it is proposed: (1) to better characterize these transgenic pigs, and (2) to explore, utilizing this animal model, potential treatments for RP.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY011498-01A1
Application #
2020082
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1997-04-01
Project End
2000-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Duke University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
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