Int J Med Sci 2020; 17(3):292-301. doi:10.7150/ijms.37804

Research Paper

Altered Long Non-coding RNAs Involved in Immunological Regulation and Associated with Choroidal Neovascularization in Mice

Liwei Zhang1,2, Huilan Zeng1,2, Jiang-Hui Wang3,4, Han Zhao1,2, Boxiang Zhang1,2, Jingling Zou1,2, Shigeo Yoshida5, Yedi Zhou1,2✉

1. Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
2. Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, China
3. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
4. Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Victoria, Australia
5. Department of Ophthalmology, Kurume University School of Medicine, Kurume, Fukuoka, Japan

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Citation:
Zhang L, Zeng H, Wang JH, Zhao H, Zhang B, Zou J, Yoshida S, Zhou Y. Altered Long Non-coding RNAs Involved in Immunological Regulation and Associated with Choroidal Neovascularization in Mice. Int J Med Sci 2020; 17(3):292-301. doi:10.7150/ijms.37804. Available from http://www.medsci.org/v17p0292.htm

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Abstract

Choroidal neovascularization (CNV) is a severe complication of the wet form of age-related macular degeneration (AMD). Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of different ocular neovascular diseases. To identify the function and therapeutic potential of lncRNAs in CNV, we assessed lncRNAs and mRNA expression profile in a mouse model of laser-induced CNV by microarray analysis. The results of altered lncRNAs were validated by qRT-PCR. Bioinformatics analyses, including Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed to clarify the potential biological functions and signaling pathways with which altered genes are most closely related. Moreover, to identify the interaction of lncRNAs and mRNAs, we constructed a coding-non-coding gene co-expression (CNC) network. By microarray analysis, we identified 716 altered lncRNAs and 821 altered mRNAs in CNV mice compared to controls. A CNC network profile based on 7 validated altered lncRNAs (uc009ewo.1, AK148935, uc029sdr.1, ENSMUST00000132340, AK030988, uc007mds.1, ENSMUST00000180519) as well as 282 interacted and altered mRNAs, and were connected by 713 edges. GO and KEGG analyses suggested that altered mRNAs, as well as those lncRNA-interacted mRNAs were enriched in immune system process and chemokine signaling pathway. Thus, lncRNAs are significantly altered in this mouse model of CNV and are involved in immunological regulation, suggesting that lncRNAs may play a critical role in the pathogenesis of CNV. Thus, dysregulated lncRNAs and their target genes might be promising therapeutic targets to suppress CNV in AMD.

Keywords: long non-coding RNA, choroidal neovascularization, angiogenesis, age-related macular degeneration, immunological regulation