RESEARCH ARTICLE


Effects of Topical Nipradilol on Early Diabetic Retinopathy in SDT Rats



Nozomi Kinoshita, Akihiro Kakehashi*, 1, Yoh Dobashi1, Ryuichiro Ono1, Fumihiko Toyoda1, Chiho Kambara1, Hiroko Yamagam1, Yusuke Kitazume2, Eiji Kobayashi3, Yasuhiro Osakabe4, Motoshige Kudo4, Masanobu Kawakami1, Yasunori Kanazawa5
1 Saitama Medical Center, Jichi Medical University, Saitama, Japan.
2 Medical Affairs Department, Kowa Pharmaceutical Company, Ltd., Japan
3 Center of Molecular Medicine, Jichi Medical University, Shimotsuke, Japan.
4 Department of Pathology, Tokyo Medical University, Tokyo, Japan.
5 Japanese Diabetes Foundation, Tokyo, Japan.


© Kinoshita et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Ophthalmology, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma, Omiya, Saitama, 330-8503, Japan. Tel: +81-48-647-2111; Fax: +81-48-648- 5188; E-mail: kakeaki@omiya.jichi.ac.jp


Abstract

We tested the effect of topical nipradilol, an antiglaucoma drug with α- and β-blocker and nitric oxide (NO) donor activities, on the early retinal changes using electron microscopy in Spontaneously Diabetic Torii (SDT) rats. In seven young male SDT rats (17 to 18 weeks old), nipradilol solution was instilled in the right eyes and nipradilol-free base solution in the left eyes three times daily for 3 months. All rats were sacrificed and both eyes were enucleated for electron microscopy at the end of the experiments. All rats had blood glucose levels exceeding 350 mg/dl within 2 weeks after the beginning of the experiment (mean final blood glucose level, 558±100.2 mg/dl). In untreated eyes of young SDT rats, the overall pathological features were almost comparable to those in older SDT rats, although the pinocytotic vesicles and free ribosomes were not as remarkable in the latter. In contrast, in nipradilol-treated eyes of SDT rats, although the basement membrane was thickened, microvilli were seen, and a larger number of electron-dense mitochondria were in the wide cytoplasm. Lipofuscin-like electron-dense granules and lamellated myelin figures also were identified. Nipradilol reduced the early morphologic changes in the endothelial cells, which reflects the metabolically active state of diabetic retinopathy in SDT rats through its action as a NO donor.

Keywords: Nipradilol, α and β -blocker, nitric oxide (NO) donor, SDT rat, diabetic retinopathy, electron microscopy.