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Y. Chen, D. J. Orlicky, V. Vasiliou; Ocular Pathologies in Knockout Mice Deficient in Glutathione and Ascorbate. Invest. Ophthalmol. Vis. Sci. 2010;51(13):709.
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Glutathione (GSH) and ascorbate are the two most abundant non-enzymatic antioxidants in the eye, which play a pivotal role in maintaining the redox homeostasis and protecting against free radical-mediated tissue damage. In addition to acting as antioxidants, both molecules have been suggested to participate in certain physiological processes. To understand the pathophysiological role of deficiencies in these major antioxidants in ocular tissues, we examined the eye histology in rodent models with deficit in GSH, ascorbate or both.
The GSH level in the cornea and lens from Gclm-/- mice was ~10% of the control level seen in Gclm+/- mice, whereas the ascorbate in the eyes from Gulo-/- mice was ~40% of the control level seen in Gulo+/- mice. Histologically, the eyes of Gclm-/- mice appeared normal when compared with that of control mice; on the other hand, the corneas from Gulo-/- mice displayed a thinner stromal layer, which is in agreement with an important role of ascorbate in collagen synthesis; interestingly, the eyes from the Gclm-/-/Gulo-/- double knockout mice revealed hypercellularity in the lens epithelium and abnormalities in the retina.
Combined deficiency in GSH and ascorbate in pre-weanling mice results in lens and retinal pathologies, indicating a significant physiological role of the interplay between these antioxidants in the eye.This project was supported, in part, by NIH grants R01 ES012463 and R01 EY017963.
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