Levels of Mature Cross-Links and Advanced Glycation End Product Cross-Links in Human Vitreous

Abstract

Purpose: To determine the levels of pyridinoline and deoxypyridinoline, two mature enzymatic cross-links, and pentosidine, an advanced glycation end product (AGE) cross-link, in the human vitreous, and to investigate the correlations among the cross-links and the effects of aging and diabetes mellitus (DM) on the levels of cross-links. Methods: Forty-five vitreous samples were collected from 32 patients (32 eyes) undergoing vitrectomy for diabetic retinopathy (DM group) and from 13 patients (13 eyes) (control group) who were age- and sex-matched patients with idiopathic macular hole or epiretinal membrane with no systemic conditions. The levels of the cross-links were determined using high-performance liquid chromatography after acid hydrolysis and pretreatment with SP-Sephadex. Results: The levels of pentosidine, pyridinoline, and deoxypyridinoline were 27.3 ± 23.1 (mean ± SD) pmol/mL (detectable in 45 of 45 specimens), 79.0 ± 40.2 ng/mL (43 of 45 specimens), and 54.0 ± 9.5 (32 of 45 specimens) ng/mL, respectively. When the vitreous samples from the DM and the control groups were compared, a significant difference (P < .05) was found in the pentosidine level but not in the levels of pyridinoline or deoxypyridinoline. No significant correlations were found between age and the cross-links. Significant correlations ( P < .01) were found among the cross-links. Conclusions: The results indicate that mature cross-link substances exist in the human vitreous. The results also suggest that glycation may occur in the vitreous after mature cross-links form and result in the formation of AGE cross-links. In human vitreous from patients with DM, increased levels of AGE cross-links may stabilize the formation of mature cross-links, but they did not increase the mature cross-links.