Protective Effect of Pemafibrate Treatment against Diabetic Retinopathy in Spontaneously Diabetic Torii Fatty Rats

• Published in: Biological & pharmaceutical bulletin Vol. 47; no. 3; pp. 713 - 722
• Main Authors: Tanaka, Yoshiaki, Takagi, Rina, Mitou, Shingen, Shimmura, Machiko, Hasegawa, Tetsuya, Amarume, Jota, Shinohara, Masami, Kageyama, Yasushi, Sasase, Tomohiko, Ohta, Takeshi, Muramatsu, Shin-ichi, Kakehashi, Akihiro, Kaburaki, Toshikatsu
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 27.03.2024; Japan Science and Technology Agency
• Subjects: Animals; Aquaporin 4; Benzoxazoles; Blood levels; Body weight; Butyrates; Cholesterol; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2; Diabetic retinopathy; Diabetic Retinopathy - drug therapy; Diabetic Retinopathy - prevention & control; Disease Models, Animal; Electroretinograms; Food consumption; High density lipoprotein; pemafibrate; Rats; Rats, Sprague-Dawley; Retina; Retinopathy; Spontaneously Diabetic Torii fatty rat model; Spontaneously Diabetic Torii fatty rat model; pemafibrate; aquaporin-4; diabetic retinopathy
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b23-00872

Diabetic retinopathy (DR) can cause visual impairment and blindness, and the increasing global prevalence of diabetes underscores the need for effective therapies to prevent and treat DR. Therefore, this study aimed to evaluate the protective effect of pemafibrate treatment against DR, using a Spontaneously Diabetic Torii (SDT) fatty rat model of obese type 2 diabetes. SDT fatty rats were fed either a diet supplemented with pemafibrate (0.3 mg/kg/d) for 16 weeks, starting at 8 weeks of age (Pf SDT fatty: study group), or normal chow (SDT fatty: controls). Normal chow was provided to Sprague–Dawley (SD) rats (SD: normal controls). Electroretinography (ERG) was performed at 8 and 24 weeks of age to evaluate the retinal neural function. After sacrifice, retinal thickness, number of retinal folds, and choroidal thickness were evaluated, and immunostaining was performed for aquaporin-4 (AQP4). No significant differences were noted in food consumption, body weight, or blood glucose level after pemafibrate administration. Triglyceride levels were reduced, and high-density lipoprotein cholesterol levels were increased. Extension of oscillatory potential (OP)1 and OP3 waves on ERG was suppressed in the Pf SDT fatty group. Retinal thickness at 1500 microns from the optic disc improved in the Pf SDT fatty group. No significant improvements were noted in choroidal thickness or number of retinal folds. Quantitative analyses showed that AQP4-positive regions in the retinas were significantly larger in the Pf SDT fatty group than in the SDT fatty group. The findings suggest that pemafibrate treatment can exert protective effects against DR.