ArticleInvestigative ophthalmology & visual science2025
A Comprehensive Analysis of Sex-Biased Gene Expression in the Aging Human Retina Through a Combination of Single-Cell and Bulk RNA Sequencing.
Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Multiomic Integration Reveals Novel miRNA-mRNA-Protein Expression Profile in the Aged Female Retina.Investigative ophthalmology & visual science · 2026Article
- Lipid-Retinoid Metabolic Network Links Genetic Variation to Molecular Heterogeneity in Inherited Retinal Degeneration.International journal of molecular sciences · 2026Article
- Endogenous oestrogens as neuroprotective modulators in the human retina: Evidence from transcriptomic profiling and aromatase inhibition.Journal of neuroendocrinology · 2026Article
- Interpretable Aging Signatures in Human Retinal Cell Types Revealed by Single-Cell RNA Sequencing and Sparse Logistic Regression.Ophthalmology science · 2026Article
- Selective deletion ofiScience · 2026Article
- Understanding TAK1 deficiency in microglia: Dual mechanisms for photoreceptor protection in a mouse model of retinitis pigmentosa.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Female sex hormones exacerbate retinal neurodegeneration.Science advances · 2025Article
- Optical coherence tomography and electroretinography in pituitary macroadenomas: a 12-month analysis by age and tumor type.Frontiers in endocrinology · 2025Observational
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Authors and funding
6 authors.
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Abstract
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.
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