Assessment of the Retinal Pigment Epithelial Cell Mosaic Based on Functional Imaging of Intracellular Pigment Dynamics in the Living Human Eye

About This Grant

Project Summary/Abstract Intracellular melanin and lipofuscin granules represent two distinct classes of photopigments found in cells of the retinal pigment epithelium (RPE). With increasing age, clinically observable decreases in RPE melanin and accumulation of RPE lipofuscin granules are typical, and specific interactions between these pigments may further lead to biogenesis of compound granules such as melanolipofuscin, reported to closely reflect the onset of age-related macular degeneration affecting an estimated 2.07 million Americans age 50 and older. A major factor limiting our knowledge of these pigment redistribution processes is the complexity of the fluorescence environment of the human retina, which has yet to be fully delineated. To address this, the objective of the proposed research is to elucidate unique spectral-temporal fluorescence signatures to determine stratification and redistribution of intracellular RPE pigment granules using a translational fluorescence lifetime imaging approach. This approach will provide fundamental insight into the connection between retinal pigment redistribution dynamics and the functional status of RPE cells by extracting spectral-temporal fluorescence signatures of retinal pigment granules (Specific Aim 1), mapping the distribution of retinal pigments in the living human eye through the development of new in vivo imaging technologies (Specific Aim 2), and tracking retinal pigment granule redistribution and modification dynamics (Specific Aim 3). By exploiting inherent properties of intracellular RPE pigments, this approach will provide fundamental insight into the role of intracellular dynamics in RPE cell function and result in the development of new imaging tools more broadly applicable to future investigations of cellular function in the living human retina. The proposed research will be performed under the guidance of Dr. Johnny Tam at the Intramural Research Program of the National Eye Institute with further career development support provided by Dr. Stephen Boppart (University of Illinois at Urbana-Champaign). During the mentored (K99) phase of the award, I will undertake specific training through the guidance of Dr. Robert Fariss (National Eye Institute), an expert in preparation and high-resolution microscopy of retinal tissue, and Drs. Alfredo Dubra (Stanford University) and Jennifer Hunter (University of Waterloo), leading experts in the development and application of AO imaging technologies, to gain expertise needed in these areas to successfully transition to an independent research career.