Molecular medicine in ophthalmic care

BACKGROUND: Lipofuscin is the most consistent and phylogenically constant morphologic marker of cellular aging. Autofluorescence of the A2E fluorophore within retinal pigment epithelial (RPE) lipofuscin affords the opportunity for noninvasive evaluation of age- and disease-related pathophysiological changes in the human retina. It is being used in National Eye Institute/Age-Related Eye Disease Study II to evaluate age-related macular degeneration (AMD) geographic atrophy expansion. Experiments show lipofuscin can be reversed in cell culture and animal models in heart, brain, spinal cord, and retinal tissues, using an array of antioxidants and iron chelators. METHODS: An 80-year-old man with a gastric resection presented with complaints of unremitting night driving difficulty despite treatment with lutein and omega III fatty acids. Notable parafoveal deposition of retinal lipofuscin by 50 fundus auto-fluorescence (580 nm excitation/660 barrier filters) and concurrent abnormalities in non-Snellen measures of visual function–Contrast Sensitivity Function, 6.5 large field tritan threshold, 10 threshold visual fields, and deficits in the National Institutes of Health/National Eye Institute Visual Function Questionnaire (VFQ) 25 subjective night driving/ mental health subscale questionnaire were obtained. The patient was placed on an over-the-counter daily oral polyphenolic mixture containing resveratrol and re-evaluated 5 months later. RESULTS: The data reveal improvements in all measures of visual function, subjective improvement in vision and mental functioning on the VFQ 25, and visible clearing of RPE lipofuscin. CONCLUSION: To our knowledge, we believe this to be the first reported human clinical case of lipofuscin reversal in the human eye correlated with measured clinical and subjective improvement in visual and mental function after nutraceutical intervention. Optometry 2009;80:695-701 Modern medicine is being ushered into molecular medicine by the mapping of the human genome and the discovery of molecules that significantly differentiate gene expression, a frontier of scientific discovery called epigenetics. Small molecules have been identified for their broad genomic effects because of their ability to enter both cell membranes and the cell nucleus to ultimately influence genetic machinery. 1,2 Small natural molecules known as polyphenols (i.e., resveratrol, quercetin, ferulic acid, curcumin, and catechin), commonly found in grapes, onions, berries, and rice bran, are notable examples of widely available over-the-counter (OTC) nutriceuticals. The impact of these molecules on gene expression, with the aim of determining how they influence human health, is a field called nutrigenomics. 3 Plants that produce these molecules are subjected to environmental stress (heat, cold, solar radiation, fungal attack), genetically up-regulating production of these defensive molecules, which are then passed on to humans when consumed in the diet, through a phenomenon called xenohormesis. 4 Hormesis then is a generally favorable biological