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C.S. Spada, R. Zuckerman, J. Burke, M. King, T. Lin, R. Tzekov, K.–M. Zhang, L.A. Wheeler; Non–Invasive Measurement of Retinal Tissue Mitochondrial Function in Space, Time and Depth in Naïve and Ocular Hypertensive Primates . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2694.
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© ARVO (1962-2015); The Authors (2016-present)
The Biometric Imaging Metabolic Mapper (Zuckerman et al. (2005), IOVS 46:4759) is the first technology that allows non–invasive measurement of mitochondrial function in space, time and depth in retinal tissue. Metabolic mapping of the retinas of naïve and ocular hypertensive (OHT) primates was performed to determine if this technology provides information that is unique, complementary or superior to that obtainable by other technologies.
Unilaterally OHT (induced by laser photocoagulation) and bilaterally naïve cynomolgus monkeys were studied. Anesthetized and immobilized monkeys were ventilated with either room air or 100% O2. The Metabolic Mapper measures fluorescence anisotropy of endogenous fluorophores and settings were employed to stimulate ganglion cells and isolate contributions from flavin adeninedinucleotide (FAD). Multifocal ERG (mfERG) employed the MFOFO paradigm (VERIS system), and optical coherence tomography (OCT) was performed with the Zeiss Stratus.
Mean fluorescence anisotropy values and its spatial distribution remained constant during repeated measurements (>20 min), whereas total fluorescence intensity decreased and its spatial distribution changed markedly. Negligible session–to–session and contralateral variability (<4%) was observed in untreated eyes. OHT caused profound depression of fluorescence anisotropy at the disc and macula (>100%) compared to naïve eyes, correlating with a 40% decrease in mfERG (global average). In OHT eyes, the instrument revealed large metabolic deficits in retinal nerve fibers at the point of exit through the lamina cribrosa and at the neuroretinal rim; OCT only revealed structural changes at the disc. Provocation with 100% O2 markedly increased metabolic values (>400%) at the macula in untreated eyes, with little change at the disc.
Metabolic mapping provides stable data that overcome the deficiencies of conventional autofluorescence imaging. In OHT, this technology provided the first evidence of functional loss in nerve fibers as they exit the lamina cribrosa.. The Metabolic Mapper revealed deficits that correlate with trends observed by mfERG, but with greater sensitivity and spatial discrimination, and also revealed functional loss inaccessible by OCT. Metabolic mapping presents a powerful new technique for early detection of functional deficits in OHT and may allow early detection of the glaucomas.
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