Effect of topical nipradilol on retinal microvascular leukocyte adhesion in diabetic rats.
BACKGROUND
Retinal leukostasis plays an important role in the pathogenesis of diabetic retinopathy.


OBJECTIVE
We studied the effects of nipradilol, a topical antiglaucoma alphabeta-blocker and nitric oxide donor, on the retinal vascular leukocyte adhesion of rats with diabetes.


METHODS
Diabetes was induced in seven Brown-Norway rats by one intravenous injection (65 mg/kg) of streptozotocin and confirmed by blood glucose levels >350 mg/dl 48 h after the injection. Nipradilol solution was instilled in the right eye and nipradilol-free base solution in the left eye for 3 weeks, after which the retinal microcirculation was evaluated by acridine orange leukocyte digital fluorography using laser scanning ophthalmoscopy. Leukocytes trapped in the retina were counted around the optic disc in a 5-disc-diameter area and compared between the right and the left eye.


RESULTS
The mean retinal leukostasis count in the nipradilol-treated eyes (19 +/- 15 cells) was significantly lower than in the untreated eyes (49 +/- 19 cells; p < 0.0008). The diameter of the retinal artery in the eyes treated with nipradilol significantly increased (111 +/- 13.5%) compared with untreated eyes (p < 0.03).


CONCLUSIONS
Topical nipradilol significantly reduced retinal leukostasis in the retinal microcirculation in diabetic rats and may be a prophylactic agent for early diabetic retinopathy through its nitric oxide donor effects on the microcirculation.
Ono
Ryuichiro
R
Department of Ophthalmology, Omiya Medical Center, Jichi Medical University, Saitama, Japan.
Kakehashi
Akihiro
A
Ito
Yuka
Y
Sugi
Norito
N
Makino
Shinji
S
Kobayashi
Eiji
E
Hakamada
Yoji
Y
Takagi
Yasuhiro
Y
Kitazume
Yusuke
Y
Kawakami
Masanobu
M
D000287:Administration, Topical; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000503:physiopathology*; D005451:Fluorescein Angiography; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology*; D018921:Leukostasis / Q000188:drug therapy / Q000503:physiopathology; D008833:Microcirculation; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000494:pharmacology; D011412:Propanolamines / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D012161:Retinal Artery / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D020030:Nitric Oxide Donors; D009883:Ophthalmic Solutions; D011412:Propanolamines; D009569:Nitric Oxide; C036089:nipradilol