A new advanced glycation inhibitor, LR-90, prevents experimental diabetic retinopathy in rats

被引：40

作者：

Bhatwadekar, A. ^{[1
]}

Glenn, J. V. ^{[1
]}

Figarola, J. L. ^{[2
]}

Scott, S. ^{[2
]}

Gardiner, T. A. ^{[1
]}

Rahbar, S. ^{[2
]}

Stitt, A. W. ^{[1
]}

机构：

[1] Queens Univ Belfast, Royal Victoria Hosp, Ctr Vis Sci, Belfast BT12 6BA, Antrim, North Ireland

[2] City Hope Natl Med Ctr, Dept Diabet & Endocrinol, Duarte, CA 91010 USA

来源：

BRITISH JOURNAL OF OPHTHALMOLOGY | 2008年 / 92卷 / 04期

关键词：

D O I：

10.1136/bjo.2007.127910

中图分类号：

R77 [眼科学];

学科分类号：

100212 [眼科学];

摘要：

Background: Diabetic retinopathy is associated with accumulation of advanced glycation end products in the retinal microvasculature. LR-90 is an effective multistage inhibitor of advanced glycation with renoprotective and anti-inflammatory properties. Aim: To explore the role of LR-90 in the progression of experimental diabetic retinopathy. Methods: Streptozotocin-induced diabetic Sprague Dawley rats were treated with LR-90 ( 50 mg/l in drinking water) for up to 32 weeks. At the end of the study, eyes were enucleated and subjected to trypsin digestion and staining with light green/haematoxylin. Acellular capillaries and pericytes were quantified in random fields using light microscopy. Results: In the LR-90-treated diabetic animals, acellular capillary numbers were reduced to 1.63 (0.20) from 2.58 ( 0.49) ( p<0.05) in diabetic controls. LR-90 treatment also restored the pericyte deficit from 18.12 (0.98) in diabetic rats to 24.19 (0.76) ( p<0.001). Conclusion: These findings show that LR-90 can effectively inhibit important lesions of diabetic retinopathy. This agent has potential for preventing retinopathy in patients with diabetes.

引用

页码：545 / 547

页数：3

共 19 条

[1]

N-epsilon-(carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins [J].

Ahmed, MU ;

Frye, EB ;

Degenhardt, TP ;

Thorpe, SR ;

Baynes, JW .

BIOCHEMICAL JOURNAL, 1997, 324 :565-570

[2]

The RAGE axis in early diabetic retinopathy [J].

Barile, GR ;

Pachydaki, SI ;

Tari, SR ;

Lee, SE ;

Donmoyer, CM ;

Ma, WC ;

Rong, LL ;

Buciarelli, LG ;

Wendt, T ;

Hörig, H ;

Hudson, BI ;

Qu, W ;

Weinberg, AD ;

Yan, SF ;

Schmidt, AM .

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2005, 46 (08) :2916-2924

[3]

AGE and RAGE inhibitors in the treatment of diabetic retinopathy [J].

Bhatwadekar, Ashay ;

Stitt, Alan W. .

EXPERT REVIEW OF OPHTHALMOLOGY, 2007, 2 (01) :105-120

[4]

Inhibition of Advanced Glycation and Absence of Galectin-3 Prevent Blood-Retinal Barrier Dysfunction during Short-Term Diabetes [J].

Canning, Paul ;

Glenn, Josephine V. ;

Hsu, Daniel K. ;

Liu, Fu-Tong ;

Gardiner, Tom A. ;

Stitt, Alan W. .

EXPERIMENTAL DIABETES RESEARCH, 2007,

[5]

Increased dicarbonyl metabolism in endothelial cells in hyperglycemia induces anoikis and impairs angiogenesis by RGD and GFOGER motif modification [J].

Dobler, Darin ;

Ahmed, Naila ;

Song, Lijiang ;

Eboigbodin, Kevin E. ;

Thornalley, Paul J. .

DIABETES, 2006, 55 (07) :1961-1969

[6]

PATHOGENESIS OF DIABETIC-RETINOPATHY [J].

ENGERMAN, RL .

DIABETES, 1989, 38 (10) :1203-1206

[7]

Anti-inflammatory effects of the advanced glycation end product inhibitor LR-90 in human monocytes [J].

Figarola, James L. ;

Shanmugam, Narkunaraja ;

Natarajan, Rama ;

Rahbar, Samuel .

DIABETES, 2007, 56 (03) :647-655

[8]

LR-90 a new advanced glycation endproduct inhibitor prevents progression of diabetic nephropathy in streptozotocin-diabetic rats [J].

Figarola, JL ;

Scott, S ;

Loera, S ;

Tessler, C ;

Chu, P ;

Weiss, L ;

Hardy, J ;

Rahbar, S .

DIABETOLOGIA, 2003, 46 (08) :1140-1152

[9]

Increased serum levels of the specific advanced glycation end product methylglyoxal-derived hydroimidazolone are associated with retinopathy in patients with type 2 diabetes mellitus [J].

Fosmark, DS ;

Torjesen, PA ;

Kilhovd, BK ;

Berg, TJ ;

Sandvik, L ;

Hanssen, KF ;

Agardh, CD ;

Agardh, E .

METABOLISM-CLINICAL AND EXPERIMENTAL, 2006, 55 (02) :232-236

[10]

Glycation and carboxymethyllysine levels in skin collagen predict the risk of future 10-year progression of diabetic retinopathy and nephropathy in the diabetes control and complications trial and epidemiology of diabetes interventions and complications participants with type 1 diabetes [J].

Genuth, S ;

Sun, WJ ;

Cleary, P ;

Sell, DR ;

Dahms, W ;

Malone, J ;

Sivitz, W ;

Monnier, VM .

DIABETES, 2005, 54 (11) :3103-3111

← 1 2 →