Data on the involvement of endothelin-1 (ET-1) in the dysregulation of retinal veins

Retinal vein occlusion (RVO) is a common vascular disease of the retina; however, the pathogenesis of RVO is still unclear. Branch RVO (BRVO) commonly occurs at the arteriovenous crossing and it was formerly believed that the diseased artery mechanically compresses the vein. However, it has been reported that the retinal vein runs deep beneath the artery at the arteriovenous crossing in eyes with an arterial overcrossing, and the venous lumen often appears to be preserved, even at the arteriovenous crossing, as shown by optical coherence tomography. Paques et al. [1] found venous nicking without arteriovenous contact using adaptive optics imaging. Thus, we investigated the potential role of a dysregulation of the retinal vein. While the pathogenesis of retinal vein occlusion (RVO) is still unclear, systemic hypertension and increased level of endothelin-1 (ET-1) are known risk factors (Flammer and Konieczka, 2015) [2]. We focused on the behavior of retinal veins in spontaneous hypertensive rats (SHR). Then, one of the retinal veins became exceptionally constricted and was nearly occluded (Fig. 1), and the chorioretinal blood flow significantly decreased in the retinas of SHRs following the intravenous injection of ET-1. In addition, immunoreactivity to ET-A receptor was higher in SHR retinas than in control (WKY; Wistar Kyoto rat) retinas (Fig. 2). The protein levels of ET-A receptor and HIF-1 were also significantly higher in SHR retinas than in WKY retinas (Fig. 3). We observed vasoactivity of retinal veins; a retinal venous constriction (Kida et al., 2018) [3]. This supports the hypothesis that ET-1 can constrict retinal veins, thus increasing retinal venous pressure, and that ET-1 may even contribute to the pathogenesis of RVO.


a b s t r a c t
Retinal vein occlusion (RVO) is a common vascular disease of the retina; however, the pathogenesis of RVO is still unclear. Branch RVO (BRVO) commonly occurs at the arteriovenous crossing and it was formerly believed that the diseased artery mechanically compresses the vein. However, it has been reported that the retinal vein runs deep beneath the artery at the arteriovenous crossing in eyes with an arterial overcrossing, and the venous lumen often appears to be preserved, even at the arteriovenous crossing, as shown by optical coherence tomography. Paques et al. [1] found venous nicking without arteriovenous contact using adaptive optics imaging. Thus, we investigated the potential role of a dysregulation of the retinal vein.
While the pathogenesis of retinal vein occlusion (RVO) is still unclear, systemic hypertension and increased level of endothelin-1 (ET-1) are known risk factors (Flammer and Konieczka, 2015) [2]. We focused on the behavior of retinal veins in spontaneous hypertensive rats (SHR). Then, one of the retinal veins became exceptionally constricted and was nearly occluded (Fig. 1), and the chorioretinal blood flow significantly decreased in the retinas of SHRs following the intravenous injection of ET-1. In addition, immunoreactivity to ET-A receptor was higher in SHR retinas than in control (WKY; Wistar Kyoto rat) retinas (Fig. 2). The protein Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/dib levels of ET-A receptor and HIF-1 were also significantly higher in SHR retinas than in WKY retinas (Fig. 3 The data is with this article and Ref. [3].

Value of the data
One of the retinal veins became exceptionally constricted and was nearly occluded, and the chorioretinal blood flow significantly decreased in the retinas of SHRs following the intravenous injection of ET-1.
The chorioretinal blood flow decreased after the intravenous injection of ET-1 in all WKYs and SHRs; however, there was a statistically significant difference in the decreases in blood flow from the baseline between WKYs ( À 7.3 7 3.0%, mean 7 S.D.) and SHRs ( À 17.3 7 8.3%) (Student's t-test; P o 0.05).
The immunoreactivity to ET-A receptor was significant in retinal vessels of the flat mount retina. In addition, it was significantly higher in SHR retinas than in WKY retinas.
The protein levels of ET-A receptor and HIF-1 were also significantly higher in SHR retinas than in WKY retinas.

Experimental design, materials and methods
To examine whether ET-1 was associated with the blood flow in the eyes of SHRs (9-11 weeks of age, n ¼ 5), the chorioretinal blood flow in the rats was assessed using laser speckle flowgraphy (LSFG) (LSFG-Micro, Softcare, Fukuoka, Japan) before and after an intravenous injection of ET-1 (2 nmol/kg) under general anesthesia. The methods and principles of LSFG have been described in a previous study. LSFG imaging provides a relative index of blood velocity represented as MBR (mean blur rate), which is determined by analyzing the blurring of the speckle pattern formed through the interference of a laser that is scattered by the movement of blood cells. In addition, retinas from SHRs and age-matched normotensive Wistar-Kyoto rats (WKYs) (n ¼ 5 each) were fixed by perfusion under deep anesthesia with a mixture of medetomidine, midazolam hydrochloride, and butorphanol tartrate. The retinal tissues were removed, and retinal sections were immunostained for