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R. Zuckerman, J. Myers, M.E. Verdugo–Gazdik, D. Markle, J. Smith, D.S. Lester; Noninvasive Measurement of Mitochondrial Function in Space, Time, and Depth in Retinal Tissue: Metabolic Mapping . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4759.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:To develop a functional imaging technology based upon the fluorescence lifetimes and anisotropy of endogenous fluorophores in mitochondria that can detect functional damage to retinal tissue prior to structural damage that can be revealed by current imaging technologies. Methods:A formal mathematical relationship was derived that permits the determination of the ultrashort fluorescence lifetimes of mitochondrial fluorophores such as FAD (lifetimes of 130 picoseconds in its monomeric form and 40 picoseconds in its dimeric form) from steady–state determinations of fluorescence anisotropy. FAD plays a key role in oxidative phosphorylation that is involved in the production of ATP that powers retinal function. Measurements of the lifetimes of FAD and NADH are related stoichiometrically to mitochondrial oxygen consumption and ATP production. Lifetime measurements based upon anisotropy measurements are insensitive to inner filtering and photobleaching effects inherent in fluorescence intensity determinations that preclude comparison of metabolism between patients and within the same patient over time. Fluorescence anisotropy determinations have been incorporated into a scanning confocal system aided by digital deconvolution techniques. The device is therefore capable of measuring mitochondrial function in space, time, and depth within human retinal tissue. Results:In a preliminary study (n=10) obtained with a prior prototype the device was able to distinguish between patients with proliferative diabetic retinopathy (PDR) and age, gender and race matched controls (P<.001). Moreover, in normals metabolic changes greater than 12 S.D. were observed when driving inner retinal tissue metabolic rate with flickered light. Ongoing more extensive clinical studies in collaboration with Wills Eye Hospital are being performed to assess the utility of metabolic mapping in early diagnosis of the glaucomas, diabetic retinopathy, and age–related macular degeneration. Data from this study will be presented. The Metabolic Mapper was developed and patented by Biometric Imaging, Inc. Conclusions:Metabolic mapping may present a powerful tool for early diagnosis of posterior segment pathologies.
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