Avascularity of the cornea is necessary for optical transparency in the visual axis. Vision-threatening corneal angiogenesis can be caused by diseases, aging, infection, or trauma. The basis of the cornea's physiological avascularity remains to be elucidated. This proposal will apply RNA interference, a promising new efficient &specific molecular technology that targets specific mRNAs, to elucidate mediators and mechanisms of normal corneal avascularity. We hypothesize that corneal avascularity is maintained at least in part by extracellular soluble VEGF receptor-1 (sVEGFR-1) Our specific aims are to test the hypotheses that: 1. To rigorously determine if adult corneal avascularity requires sFlt-1. 2. To determine whether selective genetic ablation of sFlt-1 in the corneal epithelium induces corneal vascularization. 3. To determine the expression profile of sFlt-1 in Pax6 and cornl mice with spontaneous corneal vascularization and whether sFlt-1 can restore corneal avascularity in Pax61 and cornl in these mice. This line of inquiry will have broad relevance to public health. The cornea is commonly used as a platform for testing the efficacy of anti-angiogenic therapies for use in cancer, macular degeneration, and diabetes. Understanding the molecular basis of how the cornea normally maintains its avascularity will have significant ramifications for the reliance on and validity of such anti-angiogenesis efficacy studies. Furthermore, sVEGFR-1 plays a pathogenic role in pre-eclampsia, lupus, and certain nephropathies. Our development of an siRNA against VEGFR-1 may eventually be of benefit for the management of these disorders, and it may also prove valuable in promoting beneficial angiogenesis, e.g., in stroke &heart disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY017950-03
Application #
7809473
Study Section
Anterior Eye Disease Study Section (AED)
Program Officer
Shen, Grace L
Project Start
2008-05-01
Project End
2013-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
3
Fiscal Year
2010
Total Cost
$335,239
Indirect Cost
Name
University of Utah
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
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Mukhtar, Sabrina; Ambati, Balamurali K (2018) Pediatric keratoconus: a review of the literature. Int Ophthalmol 38:2257-2266
Bowen, Randy C; Zhou, Andrew Xingyu; Bondalapati, Sailaja et al. (2018) Comparative analysis of the safety and efficacy of intracameral cefuroxime, moxifloxacin and vancomycin at the end of cataract surgery: a meta-analysis. Br J Ophthalmol 102:1268-1276
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Bondalapati, Sailaja; Ambati, Bala (2017) Intraocular foreign body removal: a novel technique using intraoperative imaging. Int Ophthalmol 37:749-752
Ambati, Balamurali (2017) Re: Schwartz et al.: Intracameral antibiotics and cataract surgery: endophthalmitis rates, cost, and stewardship (Ophthalmology. 2016;123:1411-1413). Ophthalmology 124:e42-e43
Lambert, Nathan G; ElShelmani, Hanan; Singh, Malkit K et al. (2016) Risk factors and biomarkers of age-related macular degeneration. Prog Retin Eye Res 54:64-102
Yasuma, Reo; Cicatiello, Valeria; Mizutani, Takeshi et al. (2016) Intravenous immune globulin suppresses angiogenesis in mice and humans. Signal Transduct Target Ther 1:
Bogdanovich, Sasha; Kim, Younghee; Mizutani, Takeshi et al. (2016) Human IgG1 antibodies suppress angiogenesis in a target-independent manner. Signal Transduct Target Ther 1:
Gupta, Isha; Cahoon, Judd; Zhang, Xiaohui et al. (2015) In vivo ZW800-microbead imaging of retinal and choroidal vascular leakage in mice. Exp Eye Res 134:155-8

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