Abstract
Purpose :
Myopia is the leading cause of visual impairment in the world. The sclera is critical in determining the absolute size of the eye, and thus plays a role in the development of myopia. MicroRNAs (miRNAs) involve in many physiological and pathological processes in the disease progression. The present study aimed to investigate the role of miRNAs in the development of myopia in guinea pig sclera.
Methods :
We induced a myopic guinea pig model with -10D negative lens on the right eye using 10 guinea pigs (3-week-old). Meanwhile, the left eyes were covered with plano lens and were as self-control. Before and after induction of myopia for 2 weeks, we assessed the alterations of ocular axial length and refractive error, identified the differentially expressed microRNAs in lens-induced myopic (LIM) guinea pig sclera versus fellow subject based on sequencing data, and performed the bioinformatic analysis for the differentially expressed miRNAs. Moreover, we also validated the differentially expressed miRNAs, and measured the expression of peroxisome proliferator-activated receptor α regulated by differentially expressed miRNAs at the both mRNA and protein levels.
Results :
Our results indicated that compared with LIM fellow eyes, axial length were increased whereas the refraction decreased, accompanied by statistically differences in LIM eyes. There were 27 differentially expressed miRNAs, 10 upregulated and 17 downregulated miRNAs in LIM eyes versus LIM fellow eyes. Bioinformatics analysis indicated that the miRNA-targeted genes were classified into 1108 categories, including cellular process, single-organism process, single-organism cellular process, biological regulation, metabolic process and so on. KEGG function annotation showed the signaling pathways regulated by differentially expressed miRNAs were mainly related to PPAR signaling pathway. Our Q-PCR and western blot assays also validated downregulated expressions of PPAR-α in LIM eyes.
Conclusions :
The occurrence of myopia is closely linked to the activation of multiple signaling pathways, including PPAR signaling pathway, pyruvate metabolism, propanoate metabolism, GABAergic synapse, TGF-β signaling pathway. These signaling pathways can be regulated by differentially expressed miRNAs. Our results indicate that the occurrence of myopia may be associated with metabolic imbalance.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.