July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Melatonin suppressed HIF-1α-VEGF pathway to induced retinal neovascularization and neuroglial dysfunction in an oxygen-induced retinopathy model
Author Affiliations & Notes
  • Xi Lu
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, Guangdong, China
  • Yue Xu
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, Guangdong, China
  • Yaguang Hu
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, Guangdong, China
  • Shanshan Yu
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, Guangdong, China
  • Ching-Kit Tsui
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, Guangdong, China
  • Jia Li
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, Guangdong, China
  • Xiaoling Liang
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, Guangdong, China
  • Footnotes
    Commercial Relationships   Xi Lu, None; Yue Xu, None; Yaguang Hu, None; Shanshan Yu, None; Ching-Kit Tsui, None; Jia Li, None; Xiaoling Liang, None
  • Footnotes
    Support  National Natural Science Foundation of China (No. 81670873)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5968. doi:
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      Xi Lu, Yue Xu, Yaguang Hu, Shanshan Yu, Ching-Kit Tsui, Jia Li, Xiaoling Liang; Melatonin suppressed HIF-1α-VEGF pathway to induced retinal neovascularization and neuroglial dysfunction in an oxygen-induced retinopathy model. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5968.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Anti-VEGF therapy is now a widely-used treatment for retinal neovascularization (RNV), but it's costly and may cause serious complications. This study was to investigate the effect of melatonin on RNV and neuroglia in the retina of oxygen-induced retinopathy (OIR) mice.

Methods : Neonatal C57BL/6J mice were randomly divided into four group: (1) control group: mice kept in room air (RA, 21% oxygen); (2) control + melatonin group: the age-matched mice kept in RA and administered melatonin; (3) OIR group: keeping in a 75% oxygen atmosphere from P7 to P12; (4) OIR + melatonin group: keeping in a 75% oxygen atmosphere from P7 to P12 and administered melatonin. Melatonin (10 mg/kg) was administered by intraperitoneal injection once a day from P12 to P17. Retinas for vascular leakage measurement were collected at P12, P14, P16, P18, P20, P22 and P30. Other retinas were collected and analyzed at P17. Immunofluorescence staining, immunohistochemistry staining, western blot and quantitative Real-Time PCR assays were examined.

Results : Retinal vascular leakage increased in a time manner in OIR group (*P<0.05, ***P<0.001), which reached a peak at P18. However, it reduced after melatonin treatment (#P<0.05, ##P<0.01, ###P<0.001). Besides, the size of retinal neovascular and avascular areas, the number of pre-retinal neovascular cell nuclei and the number of PCNA(+) vascular endothelial cells (VECs) in the neovascular area were decreased in mice treated with melatonin (neovascular area, 42% reduction; avascular area, 55% reduction; number of pre-retinal neovascular cell nuclei, 47% reduction; number of PCNA(+) VECs, 49% reduction, **P<0.01). After oxygen-induced injury, the density of astrocytes was decreased (***P<0.001, **P<0.01), accompanied by morphologic and functional changes of astrocytes. Besides, retinal microglia were activated (***P<0.001). Furthermore, there was an upregulation of HIF-1α and VEGF protein expression in OIR group (HIF-1α, 3.9-fold increase; VEGF, 6.9-fold increase. ***P<0.001) and an increase of RNV, which were, nevertheless, reduced by melatonin treatment (HIF-1α, 55% reduction; VEGF, 55% reduction. ###P<0.001).

Conclusions : Melatonin prevented pathologic RNV and protected neuroglial cells via inhibition of HIF-1α-VEGF pathway in OIR retinas, suggesting that melatonin could be a promising therapeutic agent for RNV.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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