Abstract

Hereditary photoreceptor degeneration is a group of blinding retinal diseases with diverse genetic origins. We propose to perform functional studies of several proteins known or postulated to have essential roles in photoreceptors. Emphasis is placed on the connecting cilium and the mammalian equivalent of a periciliary ridge complex, and their roles in membrane protein transport to the outer segment and disc morphogenesis. The proposed research will study RPGR, RPGRIP and Tubby-like proteins, hypothesized to function in the above processes. Our approaches are based on analyses of in vivo genetic models complemented by in vitro cell biological studies. The proposed efforts should contribute to our understanding of disease mechanisms underlying photoreceptor degeneration, and advance our knowledge concerning important and lesser understood aspects of photoreceptor cell biology.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY010309-11
Application #
6875567
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Dudley, Peter A
Project Start
1994-02-01
Project End
2009-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
11
Fiscal Year
2005
Total Cost
$349,000
Indirect Cost

  Institution

Name
Harvard University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Gilliam, Jared C; Chang, Juan T; Sandoval, Ivette M et al. (2012) Three-dimensional architecture of the rod sensory cilium and its disruption in retinal neurodegeneration. Cell 151:1029-41
Yang, Jun; Liu, Xiaoqing; Zhao, Yun et al. (2010) Ablation of whirlin long isoform disrupts the USH2 protein complex and causes vision and hearing loss. PLoS Genet 6:e1000955
Liu, Xiaoqing; Pawlyk, Basil S; Adamian, Michael et al. (2009) Increased light exposure alleviates one form of photoreceptor degeneration marked by elevated calcium in the dark. PLoS One 4:e8438
Yu, Hyeong Gon; Liu, Xiaoqing; Kiss, Szilard et al. (2008) Increased choroidal neovascularization following laser induction in mice lacking lysyl oxidase-like 1. Invest Ophthalmol Vis Sci 49:2599-605
Loscher, Carol J; Hokamp, Karsten; Wilson, John H et al. (2008) A common microRNA signature in mouse models of retinal degeneration. Exp Eye Res 87:529-34
Liu, Xiaoqing; Bulgakov, Oleg V; Darrow, Keith N et al. (2007) Usherin is required for maintenance of retinal photoreceptors and normal development of cochlear hair cells. Proc Natl Acad Sci U S A 104:4413-8
Storch, K-F; Paz, C; Signorovitch, J et al. (2007) Physiological importance of a circadian clock outside the suprachiasmatic nucleus. Cold Spring Harb Symp Quant Biol 72:307-18
Yang, Jun; Pawlyk, Basil; Wen, Xiao-Hong et al. (2007) Mpp4 is required for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals. Hum Mol Genet 16:1017-29
Makino, Clint L; Wen, Xiao-Hong; Michaud, Norman et al. (2006) Effects of low AIPL1 expression on phototransduction in rods. Invest Ophthalmol Vis Sci 47:2185-94
Bulgakov, Oleg V; Eggenschwiler, Jonathan T; Hong, Dong-Hyun et al. (2004) FKBP8 is a negative regulator of mouse sonic hedgehog signaling in neural tissues. Development 131:2149-59

Showing the most recent 10 out of 28 publications