Transcriptomic Analysis of Human Retina Reveals Molecular Mechanisms Underlying Diabetic Retinopathy in Sexually Divergent Manner

Today, retinopathy is one of the major causes of vision loss. With the increasing prevalence of obesity, diabetes, blood fat, and hypertension, the number of patients with retinopathy is increasing. Gender is an important factor in a variety of retinal diseases but has rarely been studied in clinical and biological studies. The current understanding of the effect of gender on molecular changes and pathways involved in the onset and progression of diabetic retinopathy (DR) is limited. This study aims to investigate the differences in Diabetic patients’ retinal gene expression between the two sexes.

Through reanalyzing publicly available RNA-sequencing data (GSE160306), comprised of 40 post-mortem samples from 20 patients with diabetic macular edema (DME) stage of DR. Totally 29 females and 11 males had been included in the dataset. In addition, samples include 20 DME patients and 20 age matched healthy controls. Differentially expressed genes (DEGs) between males and females were retrieved utilizing EdgeR package in R. Then the enrichment analysis was performed on the up-regulated genes using CluGO plugin in Cytoscape software.

Totally, in DME stage of DR 243 genes were differentially expressed (P < 0.05) between males and females comprised of 196 up-regulated and 48 down-regulated genes. Most up-regulated genes were enriched in pathways involved in Osteoclast-associated receptor (OSCAR) binds collagen and Surfactant protein D (SP-D), apoptosis, and tyrosine metabolism molecular functions.

According to the results, there are genes that are differentially expressed between male and female suffering DME cases. This suggests that disease is gender dependent. In this case the molecular mechanism underlying the disease might differ in females compared to males. For instance, the de-regulated genes in females are involved in Tyrosine metabolism, which has not been observed in males’ de-regulated pathways. Further experimental studies are suggested to validate these results