1: AMD and complement factor H (CFH). Common sequence variants of CFH have major roles in determining susceptibility to age-related macular degeneration (AMD). Using yeast 2-hybrid libraries for aged human RPE/choroid and retina and bait constructs for the AMD-related domain 7 of CFH we have identified potentially important targets for CFH binding in human RPE/choroid. These results have been confirmed by immunofluorescence localization and by using native and recombinant protein binding experiments. Mass spectroscopy is being used to identify further components of complexes that are implicated in formation of protein depositions in AMD. This has potential for drug-design to intervene in the progression of AMD. A cell-culture model for stress-related processes in AMD is also being investigated. 2: Retbindin is a novel protein of the retina. We have shown that retbindin is essentially specific for photoreceptors and that the human gene has separate cone and rod cell promoters. A transgenic mouse model shows suggests that retbindin has a role in control of retinoid and carotenoid levels in the retina. A knockout mouse has been created and is nearly ready for evaluation 3: Novel lens-specific genes with characteristics suggesting possible roles in age-related cataract have been identified and two mouse models with age-related cortical cataract have been created. 4: A miRNA cluster with high expression in eye and ear has been deleted in mouse, producing anew model of hearing and vision deficit.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAEY000433-07
Application #
8339778
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2011
Total Cost
$632,619
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Fan, Jianguo; Lerner, Joshua; Wyatt, M Keith et al. (2018) The klotho-related protein KLPH (lctl) has preferred expression in lens and is essential for expression of clic5 and normal lens suture formation. Exp Eye Res 169:111-121
Wang, Xu; Zhao, Lian; Zhang, Yikui et al. (2017) Tamoxifen Provides Structural and Functional Rescue in Murine Models of Photoreceptor Degeneration. J Neurosci 37:3294-3310
Fan, Jianguo; Jia, Li; Li, Yan et al. (2017) Maturation arrest in early postnatal sensory receptors by deletion of the miR-183/96/182 cluster in mouse. Proc Natl Acad Sci U S A 114:E4271-E4280
Rajapakse, Dinusha; Peterson, Katherine; Mishra, Sanghamitra et al. (2017) Serum starvation of ARPE-19 changes the cellular distribution of cholesterol and Fibulin3 in patterns reminiscent of age-related macular degeneration. Exp Cell Res 361:333-341
Karnati, Roy; Talla, Venu; Peterson, Katherine et al. (2016) Lacritin and other autophagy associated proteins in ocular surface health. Exp Eye Res 144:4-13
Mishra, Sanghamitra; Peterson, Katherine; Yin, Lili et al. (2016) Accumulation of cholesterol and increased demand for zinc in serum-deprived RPE cells. Mol Vis 22:1387-1404
Wyatt, M Keith; Tsai, Jen-Yue; Mishra, Sanghamitra et al. (2013) Interaction of complement factor h and fibulin3 in age-related macular degeneration. PLoS One 8:e68088