Int J Med Sci 2019; 16(4):537-547. doi:10.7150/ijms.31274 This issue

Research Paper

Microarray Analysis of Long Non-Coding RNAs and Messenger RNAs in a Mouse Model of Oxygen-Induced Retinopathy

Lusi Zhang1,2*, Xiaolin Fu1,2,3*, Huilan Zeng1,2, Jiang-Hui Wang4,5, Yingqian Peng1,2, Han Zhao1,2, Jingling Zou1,2, Liwei Zhang1,2, Yun Li1,2, Shigeo Yoshida6, Yedi Zhou1,2✉

1. Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
2. Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan 410011, China
3. Department of Ophthalmology, Hainan Western Central Hospital, Danzhou, Hainan 571799, China
4. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
5. Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Victoria, Australia
6. Department of Ophthalmology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
* These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
Zhang L, Fu X, Zeng H, Wang JH, Peng Y, Zhao H, Zou J, Zhang L, Li Y, Yoshida S, Zhou Y. Microarray Analysis of Long Non-Coding RNAs and Messenger RNAs in a Mouse Model of Oxygen-Induced Retinopathy. Int J Med Sci 2019; 16(4):537-547. doi:10.7150/ijms.31274. Available from

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Objective: Retinal neovascularization is a severe complication of many ocular diseases. To clarify the possible functions and therapeutic potential of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in retinal neovascularization, we assessed their expression profile in a mouse model of oxygen-induced retinopathy (OIR).

Methods: Microarray analysis was performed to identify altered lncRNA and mRNA expressions between OIR and control mice. The microarray results were validated by qRT-PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to determine biological functions and signaling pathways of the altered or interacted mRNAs. A coding-non-coding gene co-expression (CNC) network was constructed to identify the interaction of lncRNAs and mRNAs.

Results: We identified 198 up-regulated and 175 down-regulated lncRNAs (fold change≥2.0, P<0.05), respectively in OIR mice compared to control mice. We also identified 412 up-regulated and 127 down-regulated mRNAs (fold change≥2.0, P<0.05), respectively in OIR mice compared to control mice. GO and KEGG analyses suggested that altered mRNAs were enriched in immune system process, exopeptidase activity, ECM-receptor interaction and protein digestion and absorption. Four validated lncRNAs (ENSMUST00000165968, ENSMUST00000153785, ENSMUST00000134409, and ENSMUST00000154285) and the nearby coding gene pairs were analyzed. A CNC network profile based on those validated altered lncRNAs as well as 410 interacted mRNAs was composed of 509 connections. Moreover, the GO and KEGG analyses demonstrated that these interacted mRNAs mainly enriched in blood vessel development, angiogenesis, cell adhesion molecules and leukocyte transendothelial migration pathways.

Conclusion: Our data highlight the utility of altered lncRNA and mRNA profiling in understanding the pathogenesis of ischemia-induced retinal neovascularization and further suggest that therapeutic potential of altered lncRNA for retinal neovascularization.

Keywords: lncRNA, mRNA, microarray, expression profile, oxygen-induced retinopathy, retinal neovascularization, angiogenesis