Int J Med Sci 2019; 16(12):1652-1667. doi:10.7150/ijms.38571

Research Paper

Systematic Analysis of Transcriptomic Profile of the Effects of Low Dose Atropine Treatment on Scleral Fibroblasts using Next-Generation Sequencing and Bioinformatics

Yu-Ting Hsiao1,2, Wei-An Chang1,3,4, Ming-Tse Kuo5, Jung Lo1,5, Hsien-Chung Lin6, Meng-Chi Yen1,7, Shu-Fang Jian1, Yi-Jen Chen1,3,8✉, Po-Lin Kuo1,9✉

1. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
2. Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
3. School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
4. Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
5. Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
6. Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
7. Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
8. Department of Physical Medicine and Rehabilitation, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
9. Center for Cancer Research, Kaohsiung Medical University Kaohsiung 807, Taiwan

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Hsiao YT, Chang WA, Kuo MT, Lo J, Lin HC, Yen MC, Jian SF, Chen YJ, Kuo PL. Systematic Analysis of Transcriptomic Profile of the Effects of Low Dose Atropine Treatment on Scleral Fibroblasts using Next-Generation Sequencing and Bioinformatics. Int J Med Sci 2019; 16(12):1652-1667. doi:10.7150/ijms.38571. Available from http://www.medsci.org/v16p1652.htm

File import instruction

Abstract

This study has two novel findings: it is not only the first to deduct potential genes involved in scleral growth repression upon atropine instillation from a prevention point of view, but also the first to demonstrate that only slight changes in scleral gene expression were found after atropine treatment as side effects and safety reasons of the eye drops are of concern. The sclera determines the final ocular shape and size, constituting of scleral fibroblasts as the principal cell type and the major regulator of extracellular matrix. The aim of our study was to identify differentially expressed genes and microRNA regulations in atropine-treated scleral fibroblasts that are potentially involved in preventing the onset of excessive ocular growth using next-generation sequencing and bioinformatics approaches. Differentially expressed genes were functionally enriched in anti-remodeling effects, comprising of structural changes of extracellular matrix and metabolic pathways involving cell differentiation. Significant canonical pathways were correlated to inhibition of melatonin degradation, which was compatible with our clinical practice as atropine eye drops are instilled at night. Validation of the dysregulated genes with previous eye growth-related arrays and through microRNA-mRNA interaction predictions revealed the association of hsa-miR-2682-5p-KCNJ5 and hsa-miR-2682-5p-PRLR with scleral anti-remodeling and circadian rhythmicity. Our findings present new insights into understanding the anti-myopic effects of atropine, which may assist in prevention of myopia development.

Keywords: atropine, sclera, fibroblast, myopia, next-generation sequencing, bioinformatics, microRNA, messenger RNA