Michael H. Elliott, PhD, FARVO
Gregory L. Skuta, MD Emdowed Chair in Ophthalmology
Presbyterian Health Foundation Presidential Professor
Professor, Department of Ophthalmology
Professor, Department of Physiology
Understanding the role of membrane organization on the structure and function of retinal cells under normal and pathological conditions.
- University of Kansas, Department of Molecular Biosciences, Lawrence, KS
- University of Oklahoma Health Sciences Center, Oklahoma City, OK
1. Regulation of blood-retinal barrier permeability.
A robust and intact blood-retinal barrier is essential for normal retinal function and loss of barrier properties are pathological hallmarks of three major causes of blindness: age-related macular degeneration (AMD); diabetic retinopathy; and retinopathy of prematurity. Recent evidence from our laboratory indicates that caveolin-1, an integral protein component of specialized lipid microdomains called caveolae, is essential to maintain a normal blood-retinal barrier. We are currently using a variety of molecular, cell biological, electrophysiological, and biochemical techniques to understand the mechanism of regulation of blood-retinal barrier permeability by caveolin-1.
2. Novel modulators of ocular inflammatory responses.
Inflammation plays a critical role in the pathophysiology of retinal diseases including age-related macular degeneration, glaucoma, diabetic retinopathy, and posterior uveitis. Recent evidence outside of the eye indicates that caveolin-1 modulates inflammatory responses and innate immunity. With recently awarded Research to Prevent Blindness, Inc funding, we are examining novel regulators of local inflammatory signaling in the retina under pathological conditions.
3. Role of membrane microdomains in photoreceptor structure and function.
Cell membranes are not homogeneous and contain regions in which cellular signaling molecules are localized. The normal function of photoreceptor cells may rely on this organization for normal responses to light but this remains to be rigorously tested. A goal of the proposed experiments is to develop in vivo models to study these signaling domains and their components in a physiologically-relevant context. We have established biochemical analyses, including lipidomics and proteomics, to identify molecules that are enriched in putative membrane domains isolated from photoreceptor. We are currently examining the functional consequences of this organization on cellular function.