Tiansen LI, Ph.D.
Retinal Cell Biology and Degeneration Section
Building 6, Room 337
6 Center Drive
Bethesda, MD 20892
A second area of research is elastic fiber homeostasis in the eye and its implications for choroidal neovascularization (CNV) in age-related macular degeneration and glaucoma. A second area of our research interest involves elastic fiber homeostasis in ocular tissues mediated by LOXL1. LOXL1 polymorphism is a specific risk factor of pseudoexfoliation glaucoma (PEXG), the most common identifiable cause of open-angle glaucoma. Deposition of aggregated macromolecules in the eye and elastosis at the lamina cribrosa are hallmarks of this disease. LOXL1, a member of the lysyl oxidase family and a copper-dependent monoamine oxidase, was shown by us to be essential for elastic fiber synthesis in adult tissues. Thus impaired elastic fiber homeostasis underlies PEXG, and future challenges lie in further dissecting the disease mechanism and designing therapies. We also hypothesize that elastic fiber homeostasis has implications for AMD/CNV. The central elastic lamina of the Bruch’s membrane acts as a barrier against CNV, dramatically illustrated by angioid streaks appearing in pseudoxanthoma elasticum that develops breaks in the elastic lamina. A decline in LOXL1-mediated elastic fiber homeostasis due to advancing age could compromise the barrier function of the Bruch’s membrane and release soluble elastin-derived peptides known to promote neovascularization. Interventions aimed at promoting elastin polymer deposition may prevent or limit the aggressiveness of CNV.
The ultimate goal of our research is to find therapies for blinding retinal degenerative diseases. We look to translate new knowledge into clinical studies, whenever it becomes feasible, that can be gene or mechanism-based. Along this line, we are actively engaged in several gene replacement studies. As our studies of disease mechanisms progress, we will take advantage of the new knowledge in the design of mechanism-based therapies.
Sun X, Pawlyk B, Xu X, Liu X, Bulgakov OV, Adamian M, Sandberg MA, Khani SC, Tan MH, Smith AJ, Ali RR, Li T. Gene therapy with a promoter targeting both rods and cones rescues retinal degeneration caused by AIPL1 mutations. Gene Ther. 2010;17(1):117-31.
Yang J, Liu X, Zhao Y, Adamian M, Pawlyk B, Sun X, McMillan DR, Liberman MC, Li T. Ablation of whirlin long isoform disrupts the USH2 protein complex and causes vision and hearing loss. PLoS Genet. 2010;6(5):e1000955.
Liu C, Bakeri H, Li T, Swaroop A. Regulation of retinal progenitor expansion by Frizzled receptors: implications for microphthalmia and retinal coloboma. Hum Mol Genet. 2012;21(8):1848-60.
Sun X, Haley J, Bulgakov OV, Cai X, McGinnis J, Li T. Tubby is required for trafficking G protein-coupled receptors to neuronal cilia. Cilia. 2012;1(1):21.
Sun X, Park JH, Gumerson J, Wu Z, Swaroop A, Qian H, Roll-Mecak A, Li T. Loss of RPGR glutamylation underlies the pathogenic mechanism of retinal dystrophy caused by TTLL5 mutations. Proc Natl Acad Sci U S A. 2016;113(21):E2925-34.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
This page was last updated on August 20th, 2018