Transcriptome RNA-Seq Analysis of Normal and Keratoconus Corneal Epithelium

Abstract

Background: Keratoconus (KTCN) is a progressive eye condition characterised by thin, misshapen corneas arising in the teens or early twenties, and can cause visual disability. While this can be corrected with glasses or contact lenses, collagen cross-linking of the cornea slows disease progression. In advanced disease, patients undergo transplantation of the corneal epithelial layer with normal donor tissue. The cause of KTCN is unknown, but there is evidence for both environmental and genetic bases. Material and Methods: RNA-Seq data from published work by Kabza et al., 2017, was used to investigate the pathology of cornea tissue, analysing twenty-five KTCN and twenty-five non-KTCN samples from RNA-seq experiments. Principal component analysis plots were used to identify how characteristics impact development of keratoconus. Results: The findings show that KTCN is more common in teenagers and young adults, and all 25 KTCN samples were for individuals under 30 years old. Principal component analysis also showed that approximately 35% of samples were from individuals who rubbed their eyes. It also showed that KTCN is more common in males, representing over 65% of samples. Differential expression analysis of RNA-sequencing data was used to identify differentially expressed genes, downregulated genes were found to be enriched in many pathways, including cytokinecytokine receptor interaction pathways, and played a role in keratoconus development. Conclusion: Upregulated genes were enhanced in six pathways, including the peroxisome pathway. A potential relation was found between defects in peroxisome and keratoconus development. Overexpression of peroxisome genes increases phytanic acid levels, and causes Zellweger spectrum, affecting the cornea and potentially leading to keratoconus.