Age-related macular degeneration (ARMD) is the leading cause of vision loss in the western world. Non-neovascular ("dry") ARMD is characterized by poorly functioning retinal pigment epithelial (RPE) cells. Strategies to replace damaged RPE cells may prevent vision deterioration. Adult ciliary body epithelial cells are a patient specific, multipotent cell source that can differentiate into cells that mimic RPE cells. We intend to investigate the regulatory pathways that guide adult ciliary body progenitor cell specification into an RPE lineage. SOX2 and PAX6 are transcription factors that are attractive candidates for regulating this pathway because they are essential for normal eye development and are expressed in retinal stem cells. We intend to use transgenic mouse models to ablate or express SOX2 and PAX6 to dissect the role of these transcription factors in progenitor cell biology. My long-term scientific goal is to develop a strategy to replace damaged RPE cells for patients with non-neovascular ARMD. This project will be completed in collaboration with Dr. Larysa Pevny, an expert stem cell scientist and developmental biologist, who has significant experience in studying SOX2 and PAX6 in retinal development. In her research, she has developed the genetic tools to answer the hypotheses in this proposal and has agreed to serve as my primary mentor for this project. Drs. Patterson, Meredith, and McGahan will provide career mentorship and monitor scientific progress for the duration of this grant proposal. Their purpose will be to ensure that I am meeting incremental goals on the way to becoming an independently NIH funded physician scientist.

Public Health Relevance

We will utilize transgenic mice to study the transcriptional role and importance of SOX2 and PAX6 in adult ciliary body progenitor cells.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08EY021171-02
Application #
8228143
Study Section
Special Emphasis Panel (ZEY1-VSN (02))
Program Officer
Agarwal, Neeraj
Project Start
2011-03-01
Project End
2016-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
2
Fiscal Year
2012
Total Cost
$236,392
Indirect Cost
$17,325
Name
University of North Carolina Chapel Hill
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Ni, Aiguo; Wu, Ming Jing; Chavala, Sai H (2014) Sphere formation permits Oct4 reprogramming of ciliary body epithelial cells into induced pluripotent stem cells. Stem Cells Dev 23:3065-71
Lyles, Graham W; Moyer, Sarah; Chavala, Sai H (2012) Clinical images: peripheral retinal neovascularization in the antiphospholipid antibody syndrome. Arthritis Rheum 64:1144
Gangaputra, Sapna; Almukhtar, Talat; Glassman, Adam R et al. (2011) Comparison of film and digital fundus photographs in eyes of individuals with diabetes mellitus. Invest Ophthalmol Vis Sci 52:6168-73
Ehlers, Justis P; Chavala, Sai H; Woodward, Julie A et al. (2011) Delayed recalcitrant fungal endophthalmitis secondary to Curvularia. Can J Ophthalmol 46:199-200