DNA Aptamer Raised against Advanced Glycation End Products Prevents Abnormalities in Electroretinograms of Experimental Diabetic Retinopathy.
OBJECTIVE
Abnormalities in electroretinograms (ERG), such as reduced amplitudes and delayed implicit times of a- and b-wave and oscillatory potentials (OPs), are one of the earliest features of diabetic retinopathy prior to obvious vascular changes in diabetic retinas. We have previously shown that serum levels of advanced glycation end products (AGEs) are correlated with a delayed latency of OPs in type 2 diabetic rats. However, the pathological role of AGEs in ERG abnormalities remains unclear. We examined here whether high-affinity DNA aptamer directed against AGEs (AGE-aptamer) prevents ERG abnormalities in experimental type 1 diabetic retinopathy.


METHODS
Streptozotocin-induced diabetic rats or control rats received continuous intraperitoneal infusion of either AGE-aptamer or control aptamer via an osmotic mini pump for 16 weeks. Anthropometric, metabolic, and hemodynamic variables were measured, and an ERG was performed.


RESULTS
Although AGE-aptamer did not affect body weight, fasting and random blood glucose, HbA1c, blood pressure, or lipid parameters, it completely prevented the increase in serum AGE levels as well as the reduction of a- and b-wave and OP amplitudes in diabetic rats.


CONCLUSIONS
The present study demonstrated for the first time that AGE-aptamer prevents abnormalities in ERG in experimental diabetic retinopathy probably by blocking the harmful effects of AGEs.
Department of Ophthalmology, Kurume University School of Medicine, Kurume, Japan.
Satoshi
S
Maeda
Takanori
T
Matsui
Ayako
A
Ojima
Mika
M
Suematsu
Kuniyoshi
K
Kaseda
Yuichiro
Y
Higashimoto
Ryoji
R
Yamakawa
Sho-Ichi
S
Yamagishi
D000818:Animals; D052157:Aptamers, Nucleotide / Q000008:administration & dosage*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control; D003930:Diabetic Retinopathy / Q000517:prevention & control*; D004596:Electroretinography / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D006442:Glycated Hemoglobin / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000097:blood / Q000235:genetics*; D015918:Infusion Pumps, Implantable; D050356:Lipid Metabolism; D008297:Male; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar
D052157:Aptamers, Nucleotide; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced