The metabolism of drug and arachidonic acid (AA) by diabetic rat ocular tissues was studied Little information is available on drug metabolism enzymes in ocular tissues. I investigated the presence of various cytochrome P-450 isoenzymes by
measuring
different drug metabolizing enzymes i.e, 7-ethoxycoumarin-0-dethylase and benzphetamine demethylase activities in cornea and choroid retina or sclera.
This results demonstrate that choroid, retina or sclera possess the highest activities of drug metabolizing enzymes, The highest activities of 7-ethoxycoumarin-0-deethylase and benzphetamine demethylase were found in choroid, retina or sclera.
The
highest activities of drug metabolizing enzymes is accompanied by high activity of NADPH cytochrome P-450(C) reductase, an integral component of this enzyme study. The choroid, retina or sclera possesses the high activity of metabolizing
arachidonic
acid to biologically active compounds, whereas the cornea has low activity of metabolizing arachidonic acid. A form of cytochrome P-450 has appear rat ocular tissues in diabetes and the effect of diabetes on ocular tissues cytochrome P-450
expression
can be reversed by insulin treatment.
The specialized location of cytochrome P-450 isozymes in ocular tissues suggests a physiological function related to activation of endogenous compounds such as arachidonic acid, in addition to detoxifiaction related to activation of endogenous
compounds
such as arachidonic acid, in addition to detoxifiaction of drugs. Thus the choroid, retina or sclera is the site of metabolism and detoxification of drugs are carried to ocular tissues via circulating blood.
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