Comparative Proteomics Analysis of the Postmitochondrial Supernatant Fraction of Human Lens-Free Whole Eye and Liver

The increasing incidence of ocular diseases has accelerated research into therapeutic interventions needed for the eye. Ocular enzymes play important roles in the metabolism of drugs and endobiotics. Various ocular drugs are designed as prodrugs that are activated by ocular enzymes. Moreover, ocular enzymes have been implicated in the bioactivation of drugs to their toxic metabolites. The key purpose of this study was to compare global proteomes of the pooled samples of the eye (n = 11) and the liver (n = 50) with a detailed analysis of the abundance of enzymes involved in the metabolism of xenobiotics and endobiotics. We used the postmitochondrial supernatant fraction (S9 fraction) of the lens-free whole eye homogenate as a model to allow accurate comparison with the liver S9 fraction. A total of 269 proteins (including 23 metabolic enzymes) were detected exclusively in the pooled eye S9 against 648 proteins in the liver S9 (including 174 metabolic enzymes), whereas 424 proteins (including 94 metabolic enzymes) were detected in both the organs. The major hepatic cytochrome P450 and UDP-glucuronosyltransferases enzymes were not detected, but aldehyde dehydrogenases and glutathione transferases were the predominant proteins in the eye. The comparative qualitative and quantitative proteomics data in the eye versus liver is expected to help in explaining differential metabolic and physiologic activities in the eye. SIGNIFICANCE STATEMENT Information on the enzymes involved in xenobiotic and endobiotic metabolism in the human eye in relation to the liver is scarcely available. The study employed global proteomic analysis to compare the proteomes of the lens-free whole eye and the liver with a detailed analysis of the enzymes involved in xenobiotic and endobiotic metabolism. These data will help in better understanding of the ocular metabolism and activation of drugs and endobiotics.

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