LncRNAs are involved in the pathogenesis of diabetic retinopathy through the modulation of multiple pathogenetic pathways

Purpose Long non-coding RNAs (lncRNAs) are broadly classified as transcripts longer than 200 nucleotides. LncRNAs-mediated biology has been implicated in a variety of cellular processes and human diseases. Diabetic retinopathy (DR) is one of the leading causes of blindness. However, little is known about their roles in DR. The aim of this study aimed to identify lncRNAs involved in early DR and characterize their roles in DR pathogenesis.

Researcheras at the Nanjing Medical University, China established a mouse model of streptozotocin (STZ)-induced diabetes, and performed lncRNAs expression profiling of retinas using microarray analysis. Based on the Pearson correlation analysis, lncRNAs/mRNAs co-expression network was constructed. GO enrichment and KEGG analysis of lncRNAs-co-expressed mRNAs was conducted to identify the related biological modules and pathologic pathways. Real-time PCR was conducted to detect the expression pattern of lncRNA in the clinical samples and RF/6A cell model of hyperglycemia.

Approximately 303 lncRNAs were aberrantly expressed in the retinas of early DR, including 214 down-regulated lncRNAs and 89 up-regulated lncRNAs. GO analysis indicated that these lncRNAs-co-expressed mRNAs were targeted to eye development process (ontology: biological process), integral to membrane (ontology: cellular component), and structural molecule activity (ontology: molecular function). Pathway analysis indicated that lncRNAs-co-expressed mRNAs were mostly enriched in axon guidance signaling pathway. In addition, MALAT1, a conserved lncRNA, was significantly up-regulated in RF/6A cell model of hyperglycemia, in the aqueous humor samples and fibrovascular membranes of diabetic patients.

The researchers conclude that LncRNAs are involved in the pathogenesis of DR through the modulation of multiple pathogenetic pathways. MALAT1, a conserved lncRNAs, may become a potential therapeutic target for the prognosis, diagnosis and treatment of DR.

• Yan B, Tao Z, Li XM, Zhang H, Yao J, Qin J. (2014) Aberrant expression of long non-coding RNAs in early diabetic retinopathy. Invest Ophthalmol Vis Sci [Epub ahead of print]. [abstract]