Makiko Katagiri1, Jun Shoji2, Noriko Inada2, Satoshi Kato3, Shigehiko Kitano4, Yasuko Uchigata5. 1. Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. makikokumakawa@gmail.com. 2. Division of Ophthalmology, Department of Visual Sciences, Nihon University School of Medicine, Tokyo, Japan. 3. Department of Ophthalmology, The University of Tokyo, Tokyo, Japan. 4. Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. 5. Department of Medicine, Diabetes Center, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
Abstract
BACKGROUND/AIMS: Glyceraldehyde-derived advanced glycation end products (glycer-AGE; also called Toxic-AGE [TAGE]) play a crucial role in the pathogenesis of diabetic angiopathy. However, the relationships between vitreous glycer-AGE levels and diabetic retinopathy (DR) severity, and between glycer-AGE levels and the levels of other angiogenic factors remain unknown. We investigated the correlation between levels of vitreous biomarkers, including glycer-AGE and angiogenic factors (vascular endothelial growth factor [VEGF], interleukin [IL]-8, leptin, placental growth factor [PlGF], endoglin, and fibroblast growth factor [FGF]-2) in patients with DR, using three DR staging groups. METHODS: In this cross-sectional study, we examined 33 eyes from 33 patients with diabetes mellitus who underwent a vitrectomy (non-proliferative DR [NPDR, n = 8]; PDR with simple vitreous haemorrhage [VH, n = 17]; or PDR with a fibrovascular proliferative membrane [FVM, n = 8]). Vitreous levels of glycer-AGE and VEGF were evaluated using enzyme-linked immunosorbent assays. Vitreous levels of IL-8, leptin, PlGF, endoglin, and FGF-2 were evaluated using beaded assay methods. RESULTS: Vitreous levels of glycer-AGE in the FVM group were significantly higher than those in the NPDR and VH groups (all p < 0.05). Vitreous levels of VEGF (r = 0.85, p = 1.7 × 10-6) and leptin (r = 0.60, p = 5.0 × 10-3) were significantly correlated with levels of PlGF. CONCLUSION: The two systems (VEGF-PlGF-leptin and glycer-AGE) were represented in these measured biomarkers. High vitreous levels of both VEGF and glycer-AGE may be linked to more severe DR, suggesting that anti-VEGF and anti-TAGE therapy may be an important part of the therapeutic strategy for DR.
BACKGROUND/AIMS: Glyceraldehyde-derived advanced glycation end products (glycer-AGE; also called Toxic-AGE [TAGE]) play a crucial role in the pathogenesis of diabetic angiopathy. However, the relationships between vitreous glycer-AGE levels and diabetic retinopathy (DR) severity, and between glycer-AGE levels and the levels of other angiogenic factors remain unknown. We investigated the correlation between levels of vitreous biomarkers, including glycer-AGE and angiogenic factors (vascular endothelial growth factor [VEGF], interleukin [IL]-8, leptin, placental growth factor [PlGF], endoglin, and fibroblast growth factor [FGF]-2) in patients with DR, using three DR staging groups. METHODS: In this cross-sectional study, we examined 33 eyes from 33 patients with diabetes mellitus who underwent a vitrectomy (non-proliferative DR [NPDR, n = 8]; PDR with simple vitreous haemorrhage [VH, n = 17]; or PDR with a fibrovascular proliferative membrane [FVM, n = 8]). Vitreous levels of glycer-AGE and VEGF were evaluated using enzyme-linked immunosorbent assays. Vitreous levels of IL-8, leptin, PlGF, endoglin, and FGF-2 were evaluated using beaded assay methods. RESULTS: Vitreous levels of glycer-AGE in the FVM group were significantly higher than those in the NPDR and VH groups (all p < 0.05). Vitreous levels of VEGF (r = 0.85, p = 1.7 × 10-6) and leptin (r = 0.60, p = 5.0 × 10-3) were significantly correlated with levels of PlGF. CONCLUSION: The two systems (VEGF-PlGF-leptin and glycer-AGE) were represented in these measured biomarkers. High vitreous levels of both VEGF and glycer-AGE may be linked to more severe DR, suggesting that anti-VEGF and anti-TAGE therapy may be an important part of the therapeutic strategy for DR.
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