IDENTIFICATION OF LUTEIN AND ZEAXANTHIN OXIDATION-PRODUCTS IN HUMAN AND MONKEY RETINAS

Purpose. To characterize fully all the major and minor carotenoids and their metabolites in human retina and probe for the presence of the o xidative metabolites of lutein and zeaxanthin. Methods, Carotenoids of a composite of 58 pairs of human retinas and a monkey retina were elu cidated by comparing their high-performance liquid chromatography (HPL C)-ultraviolet/visible absorption spectrophotometry (UV/Vis)-mass spec trometry (MS) profile with those of authentic standards prepared by or ganic synthesis. Results. In addition to lutein and zeaxanthin, severa l oxidation products of these compounds were present in the extracts f rom human retina. A major carotenoid resulting from direct oxidation o f lutein was identified as 3-hydroxy-beta,epsilon-caroten-3'-one. Mino r carotenoids were identified as: 3'-epilutein,epsilon ,epsilon-carote ne-3,3'-diol, epsilon,epsilon-carotene-3,3'-dione, 3'-hydroxy-epsilon, epsilon-caroten-one, and 2,6-cyclolycopene-1,5-diol. Several of the ge ometric isomers of lutein and zeaxanthin were also detected at low con centrations. These were as follows: 9-cis-lutein, 9'-cis-lutein, 13-ci s-lutein, 13'-cis-lutein, 9-cis-zeaxanthin, and 13-cis-zeaxanthin. Sim ilar results were also obtained from HPLC analysis of a freshly dissec ted monkey retina. Conclusions. Lutein, zeaxanthin, 3'-epilutein, and 3-hydroxy-beta,epsilon-caroten-3'-one in human retina may be interconv erted through a series of oxidation-reduction reactions similar to our earlier proposed metabolic transformation of these compounds in human s. The presence of the direct oxidation product of lutein and 3'-epilu tein (metabolite of lutein and zeaxanthin) in human retina suggests th at lutein and zeaxanthin may act as antioxidants to protect the macula against short-wavelength visible light. The proposed oxidative-reduct ive pathways for lutein and zeaxanthin in human retina, may therefore play an important role in prevention of age-related macular-degenerati on and cataracts.