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D.M. Meisler, T. Koeck, J.T. Connor, K.S. Aulak, B.H. Jeng, J.G. Hollyfield, D.J. Stuehr; Inhibition of Nitric Oxide Synthesis in Corneas in Corneal Storage Media . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4706.
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Purpose: To determine if nitric oxide synthesis by human corneas can be inhibited during corneal storage. Methods: 1.0 mM of monomethyl-L-arginine (LMMA), a nitric oxide synthase inhibitor, was added to four chambers of Optisol GS corneal storage media, each containing a viable human corneal button. Each chamber was sampled (0.4 ml) for baseline measurements and at one-day intervals for 21 days. Four chambers of Optisol GS corneal storage media, each containing companion corneas to the corneas exposed to LMMA served as controls and were sampled in tandem with the LMMA-containing chambers. An unused vial of Optisol GS corneal storage media served as a background media control. The total amount of nitrate and nitrite (stable breakdown products of nitric oxide) in each sample was determined using a spectrophotometric method based on the Greiss reaction. A polynomial random coefficients model, fitting Concentration on linear, quadratic, cubic, and square-roots terms times time in Days, was fit. The derivative of the fitted equation was also investigated to estimate rates of accumulation over time. Results: Data from the daily sampling of LMMA-containing media showed a statistically marked reduction in the rate of accumulation of nitrate and nitrite concentrations, as compared to controls (p<0.01), up until Day 10 when the rates became and remained equivalent. There was a marked reduction in the levels of nitrate and nitrite accumulation in the study chambers as compared to control chambers for each time point during the course of the study (p<0.01, e.g. 1.03 µM 95% CI 0.92-1.16 µM at 10 days). There was also a substantial delay (3 days) in the rise of nitrate and nitrite concentration in the study group. Accumulation rates were more than 0.15 µM/day higher for the first three days in the media without LMMA. No nitrate and nitrite were detected in the background media control sample. Conclusions: The progressive increase in nitrate and nitrite accumulation in corneal storage media can be delayed and blunted by the addition of a nitric oxide synthase inhibitor. Given the toxic free radical properties of nitric oxide, corneas in storage awaiting transplantation may benefit from having a nitric oxide synthase inhibitor added to storage media.
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