The pathogenesis of age-related macular degeneration (AMD) is unknown, but clinical evidence strongly suggests that the lesion resides in the retinal pigment epithelium (RPE). The progression of the disease is temporally and spatially related to the intracellular deposition of the fluorescent """"""""age pigment"""""""", or lipofuscin, in the RPE, and it has been hypothesized that lipofuscin contributes to the pathogenesis of AMD. The role of lipofuscin is actively being investigated in biochemical and morphological studies; a noninvasive method for measuring lipofuscin will extend these efforts to clinical studies. Preliminary studies demonstrate that noninvasive measurements of retinal fluorescence is possible and that this fluorescence exhibits spatial and spectral patterns consistent with lipofuscin being the major fluorophore. A noninvasive method for measuring lipofuscin in normal subjects and in patients with AMD may help determine whether lipofuscin plays an important role in the development of degenerative diseases such as AMD.
The specific aims are: (1) Develop a fluorophotometric method for noninvasive determination of lipofuscin in the RPE. The method will account for absorption by the crystalline lens, the macular yellow pigment, and RPE melanin. (2) Perform human measurements to test and optimize the method and to determine the relative contribution of other ocular fluorophores. Perform pilot studies in subjects selected to cover a broad range of ocular melanin, lens turbidity, and age. (3) Compare noninvasive measurements of lipofuscin in primate eyes with values obtained from cryostat sections of the same RPE. (4) Characterize lipofuscin accumulation in a population of normal Caucasian subjects, and correlate lipofuscin levels with age, macular pigment density, crystalline lens density, and iris pigmentation. (5) In patients with AMD, determine lipofuscin levels and correlate them with age, presence of drusen, and extent of degeneration. Determine whether atrophic regions are bounded by regions of elevated lipofuscin, and whether extreme levels of lipofuscin identify retinal regions at risk for subsequent atrophy and/or neovascularization.
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