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Ram H Nagaraj, Stefan Rakete, Johanna Rankenberg, Levi Bonnell, Brandie Wagner, Anne Lynch, Christian Henning, Marcus Glomb; Advanced Glycation Endproducts in capsulorhexis specimen: Correlation with Diabetic Retinopathy.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):97.
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© ARVO (1962-2015); The Authors (2016-present)
Long-term diabetes leads to several pathologies in the eye that include cataract formation and diabetic retinopathy (DR). In diabetes, elevated glucose levels combined with increased oxidative stress lead to formation of Advanced Glycation Endproducts (AGEs) through reactive α-dicarbonyl intermediates. The AGE accumulation is more prominent in tissues with negligible protein turnover rate, such as lens capsule. We reasoned that AGE levels in capsulorhexis specimen (a portion of the anterior lens capsule) removed during routine cataract surgery would provide an ideal tissue to evaluate the long-term effects of diabetes on the development of complications, such as DR. Thus, the purpose of this study was to establish whether the capsule AGE levels are elevated in diabetes and whether they correlate with the presence of DR.
Fifty-eight consented cataract patients, consisting of 19 diabetics without DR, 10 diabetics with DR and 29 non-diabetics, participated in this study. The capsulorhexis specimen were cleared from adherent lens protein and cells, and subjected to extensive enzymatic digestion to release free AGEs. The samples were then analyzed by a UPLC-MS/MS multimethod. The identified AGEs were quantified using authentic reference compounds.
Our method was capable of simultaneously measuring 30 AGEs. In our samples 15 of the 30 AGEs were clearly identified. Among those AGEs, levels of DT-Ha, glusosepane and CEL were significantly higher in diabetics (all p=0.05) compared to non-diabetics. The levels of glucosepane (p=0.13) and DT-Ha (p=0.39) were elevated in diabetic patients with DR compared to the other two groups, although not significantly.
These preliminary results suggest that the levels of several AGEs are elevated in capsulorhexis specimen of diabetic patients relative to non-diabetics and that two AGEs are further elevated in patients with DR. Thus, the results suggest that the capsulorhexis AGEs could be used as surrogate markers for DR, and possibly for other long-term complications of diabetes. The capsule AGE levels might also prospectively predict the development of secondary cataracts.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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