This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our data suggest that the relative hypoxia in the fluids around the lens is important to protect the lens against the most common type of age-related cataract. Destruction of the vitreous gel leads to increased exposure of the lens to oxygen and the formation of nuclear cataracts. We detected oxygen gradients in the eyes of patients undergoing retinal surgery that predicted that the vitreous body must be consuming oxygen. Direct tests of oxygen consumption in isolated vitreous humor confirmed this predication and demonstrated that this effect was independent of cellular metabolic activity and dependent on ascorbate. Previous studies in rabbits have suggested that ascorbate enters the eye in the aqueous humor that nourishes the structures of the anterior of the eye (ascorbate concentrations in aqueous humor are >20X greater than in the blood). It was believed that ascorbate in the posterior of the eye was derived by diffusion from the aqueous humor. However, unlike other species, humans have higher ascorbate in the vitreous humor (in the posterior of the eye) than in the (anterior) aqueous humor, ruling out the aqueous as the sole source of ascorbate for the human vitreous. To get a better idea of the ascorbate distribution in the eye and, therefore, the sources and sinks for ascorbate, we would like to measure ascorbate gradients in the eyes of living rabbits and humans.
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