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Updated: Jun 2, 2025
Single-cell Profiling of Developing and Mature Retinal Neurons
Published on: April 19, 2012
A Comprehensive Analysis of Sex-Biased Gene Expression in the Aging Human Retina Through a Combination of Single-Cell
Hongling Liu1,2, Xue Zhang1,2, Qing Wang1,2
1Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Purpose:
Previous studies have reported divergent sexual responses to aging; however, specific variations in gene expression between aging males and females and their potential association with age-related retinal diseases remain unclear. This study collected data from public databases and developed a comprehensive comparison of retina between aging females and males.
Methods:
Single-cell RNA (scRNA) and bulk RNA sequencing data of the aging retina from females and males in public databases were utilized for integrated analysis to investigate sex-biased expression in retina. Additionally, in vitro experiments were conducted on individuals with retinitis pigmentosa (RP) to validate the sex difference in degenerative retina.
Results:
Bulk RNA analysis revealed sex-biased expression of specific genes in retina of aging individuals, with immune pathway-related genes exhibiting higher expression in females compared to males. The scRNA analysis demonstrated that sex-biased gene expression was cell-type specific in aging retina. Furthermore, susceptibility genes for age-related macular degeneration and RP exhibited variation across different cell types and sexes. Cell-to-cell communication unveiled an increased interaction associated with TGFB1, CCL7, and VEGFA in Müller glia, microglia, and astrocytes of female retina. Notably, we observed female-biased chemokine expression in microglia contributing to heightened susceptibility to immune inflammation in female retina. Finally, we confirmed a more pronounced inflammatory response during degeneration in female rd10 mouse retina compared to males.
Conclusions:
This study provides a comprehensive comparison of retina between females and males in healthy aging human retina and highlights the significance of sex as an influential factor in retinal diseases.
