Advanced Glycation End Product Accumulation in Subjects with Open-Angle Glaucoma with and without Exfoliation

Abstract

Advanced glycation end products (AGEs), which are the products of a non-enzymatic reaction between reducing sugars and other macromolecules, are critical in aging, as well as metabolic and degenerative diseases. To assess the involvement of AGEs in glaucoma, skin autofluorescence (sAF) level, which is a measurement of AGEs’ accumulation, was compared among Japanese patients with glaucoma (316 with primary open-angle glaucoma (PG) and 127 exfoliation syndrome and glaucoma (EG)) and controls (133 nonglaucomatous controls) (mean age 71.6 ± 12.8 years, 254 men and 322 women). The sAF values were estimated from the middle fingertip using a 365 nm light-emitting diode for excitation and detection at 440 nm emission light. The estimated AGE values (arbitrary unit) were 0.56 ± 0.15, 0.56 ± 0.11, and 0.61 ± 0.11 in the control, PG, and EG groups, respectively (p < 0.0001, analysis of variance); and were significantly higher in the EG group than the control (p = 0.0007) and PG (p < 0.0001) groups. After adjustment for various demographic parameters by multivariate analyses, male sex (standard β = 0.23), EG (0.19), and diabetes (0.09) were associated with higher AGE levels; PG (−0.18) and smoking (−0.19) were associated with lower AGE levels. Age, visual acuity, intraocular pressure, glaucoma medications, lens status, and systemic hypertension were not associated with AGEs. The high AGE level in EG suggested that specific oxidation and glycation mechanisms underlie the glaucoma pathogenesis associated with pseudoexfoliation syndrome.

Fingertip-Measured Skin Carotenoids and Advanced Glycation End Product Levels in Glaucoma

“…Significant differences in AGEs were observed by glaucoma type, with higher AGEs in EG and lower AGEs in PG ( Table 8 ). The result of AGEs in EG was consistent with our previous report [ 40 ]. Exfoliation products are produced by the aggregation of microfibrils [ 50 ], and the effect of AGEs via RAGE may enhance the production.…”

“…Upregulation of RAGE might cause early cell death of the RCGs [ 39 ]. AGEs levels were also measured percutaneously by the previously reported procedure using fingertip-measured skin autofluorescence (sAF) [ 40 ]. Among the AGEs, Nε-(carboxymethyl)-lysine (CML) was considered to be strongly involved in the pathogenic role, but it was difficult to detect directly because of the nonfluorescent feature of CML.…”

“…As part of our ongoing research program directed toward the analysis of the relationship between ophthalmologic disorders and stress markers measured by fingertip measurements [ 16 , 17 , 18 ], we investigated the clinical factors including SC and AGEs levels with glaucoma types. We previously reported AGEs levels in PG and EG [ 40 ]; however, the relationship between SC levels and glaucoma has not been reported. Herein, we report a comparison of the SC and AGEs levels in patients with and without glaucoma.…”

From Oxidative Stress to Inflammation in the Posterior Ocular Diseases: Diagnosis and Treatment

“…The vascular dysfunction and neurodegeneration at the retina might be mediated by advanced glycation end products (AGEs), which are an oxidative stress-related biomarker that results from the reaction between reducing sugar with amino groups in proteins, lipids, or nucleic acids and is detected in the axons of RGCs and retinal glial cells in glaucoma. AGEs might activate signaling molecules as mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-kB), which induces ROS production, and the subsequent angiogenesis and neural apoptosis, which are related to immune responses as further described below [ 71 ]. In this way, Hondur et al reported that AGEs were higher in aqueous humor and blood samples in glaucomatous patients than in non-glaucomatous healthy patients [ 60 ].…”

“…Hondur et al [ 60 ] reported significantly higher levels of AGEs in blood and aqueous humor (AH) samples in glaucomatous patients compared to control. AGEs accumulation can also be detected using a sensor that determines the skin autofluorescence levels, which is correlated with AGEs [ 71 ].…”