Angiotensin II receptor blocker inhibits abnormal accumulation of advanced glycation end products and retinal damage in a rat model of type 2 diabetes.
The effects of an angiotensin II receptor blocker (ARB) on the accumulation of one of advanced glycation end products (AGEs), pentosidine, expression of vascular endothelial growth factor (VEGF) and retinal function were investigated in Spontaneously Diabetic Torii (SDT) rats. Candesartan, an ARB, was administered to SDT rats from 10 to 44 weeks of age and the results compared with untreated SDT rats and SD rats. Electroretinograms (ERGs) were recorded to evaluate retinal function. At 44 weeks of age, pentosidine was quantified in the vitreous, lens and plasma using high-performance liquid chromatography (HPLC). Real-time reverse transcription-PCR (RT-PCR) analysis was also performed in order to measure VEGF mRNA expression in the retina. Histological changes were examined and immunohistochemistry for pentosidine performed on the retina and retinal microvasculature. In untreated SDT rats, the amplitudes of a- and b-waves, oscillatory potentials were reduced significantly at 44 weeks of age compared with the 10-week levels, whereas they remained unchanged in SDT rats treated with candesartan. The concentration of pentosidine in the vitreous and lens did not change in treated SDT rats but increased in untreated SDT rats. Retinal VEGF mRNA expression was inhibited in treated SDT rats. Histologically, proliferative tissue was detected around the optic disc, with pentosidine being detected only in untreated SDT rats. Our findings indicate the ARB may inhibit the development of diabetic retinopathy by reducing the accumulation of pentosidine, one of AGEs and expression of VEGF in the retina.
Department of Ophthalmology, Osaka Medical College, Daigaku-machi 2-7, Takatsuki, Osaka 569-8686, Japan. tsugiyama@poh.osaka-med.ac.jp
Tetsuya
T
Sugiyama
Takashi
T
Okuno
Masayuki
M
Fukuhara
Hidehiro
H
Oku
Tsunehiko
T
Ikeda
Hiroshi
H
Obayashi
Mitsuhiro
M
Ohta
Michiaki
M
Fukui
Goji
G
Hasegawa
Naoto
N
Nakamura
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D001562:Benzimidazoles / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004353:Drug Evaluation, Preclinical; D004596:Electroretinography; D005786:Gene Expression Regulation / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013777:Tetrazoles / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
D047228:Angiotensin II Type 1 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D013777:Tetrazoles; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D001120:Arginine; C062187:pentosidine; D008239:Lysine; C077793:candesartan cilexetil