α-Melanocyte-stimulating hormone inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy

Authors:Yang Qianhui,  Zhang Yan,  Bo Qiyu,  Cao Yunshan,  Yang Wei,  Wang Fei,  Li Xiaorong
DOI: 10.3760/cma.j.issn.2095-0160.2016.12.004
Published 2016-12-10
Cite as Chin J Exp Ophthalmol, 2016,34(12): 1072-1076.

Abstract

Background

Retinal neovascularization (RNV) occurs in multiple eye diseases, which can lead to bleeding and retinal detachment.Therefore, inhibition of pathological RNV is becoming crucial to the treatment of ocular diseases.Research has shown that α-melanocyte-stimulating hormone (α-MSH) inhibits retinal angiogenesis during physiological development; however, the effects of α-MSH on pathological RNV remain unknown.

Objective

This study was to investigate the effects of intravitreal injection of α-MSH at different concentrations on pathological RNV in a mouse model of oxygen-induced retinopathy (OIR).

Methods

Forty healthy clean C57BL/6J mice were randomly divided into OIR+ 0.33 μg/μl α-MSH, OIR+ 1.67 μg/μl α-MSH, OIR+ 3.30 μg/μl α-MSH, OIR, and normal control groups at postnatal day 7 (P7), with 8 pups in each group.The α-MSH intervention groups and OIR group were exposed to high oxygen (75±2)% for 5 days, then maintained under normal air condition for another 5 days; whereas the normal control group was raised under normoxia for 10 days.Retro-orbital injection of high molecular weight fluorescein isothiocyanate-dextran (FITC-dextran) was performed on P17 mice.The retina whole mounts were prepared to reveal retinal vasculature and quantify relative area of vessel obliteration.The mouse eyeballs were subjected to paraffin sections and hematoxylin-eosin staining, and the average number of pre-retinal nuclei per section was quantified.

Results

FITC-dextran labeled retinal whole mounts showed that the relative vessel obliteration area in normal control, OIR, OIR+ 0.33 μg/μl α-MSH, OIR+ 1.67 μg/μl α-MSH, and OIR+ 3.30 μg/μl α-MSH groups were (0.00±0.00)%, (23.01±3.39)%, (18.14±7.20)%, (15.64±7.07)%, and (7.62±6.52)%, respectively.There was a statistical significance in the relative avascular area among the groups (F=19.635, P<0.05). The relative avascular area in the OIR group was significantly higher than that in the OIR+ 3.30 μg/μl α-MSH group (t=4.293, P<0.01). The results of histopathological examinations showed that the average number of pre-retinal nuclei per section in normal control, OIR, OIR+ 0.33 μg/μl α-MSH, OIR+ 1.67 μg/μl α-MSH, and OIR+ 3.30 μg/μl α-MSH groups were 0.00±0.00, 11.45±4.26, 6.35±2.34, 4.96±1.79 and 1.03±1.25, respectively.There was a statistical significance in the average number of pre-retinal nuclei per section among the groups (F=147.87, P<0.05). The average number of pre-retinal nuclei per section in the OIR group was significantly higher than that in the OIR+ 0.33 μg/μl α-MSH, OIR+ 1.67 μg/μl α-MSH, and OIR+ 3.30 μg/μl α-MSH groups, the differences between the groups had statistical significances (all at P<0.001).

Conclusions

α-MSH reduces the relative area of vessel obliteration and the average number of pre-retinal nuclei in the retinas of OIR mouse model.The inhibitory effects of α-MSH on the pathological RNV are dose-dependent.

Key words:

Oxygen-induced retinopathy; Retinal neovascularization; α-Melanocyte-stimulating hormone

Contributor Information

Yang Qianhui
Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin 300384, China
Zhang Yan
Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin 300384, China
Bo Qiyu
Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin 300384, China
Cao Yunshan
Department of Ophthalmology, Gansu Provincial Hospital, Lanzhou 730000, China
Yang Wei
Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin 300384, China
Wang Fei
Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin 300384, China
Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin 300384, China
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Updated: September 24, 2019 — 1:49 am