June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
The the Influence of Sex on the Aging Lens Transcriptome
Author Affiliations & Notes
  • Adam Faranda
    University of Delaware, Newark, Delaware, United States
  • Mahbubul H. Shihan
    University of Delaware, Newark, Delaware, United States
  • Yan Wang
    University of Delaware, Newark, Delaware, United States
  • Melinda K Duncan
    University of Delaware, Newark, Delaware, United States
  • Footnotes
    Commercial Relationships   Adam Faranda, None; Mahbubul Shihan, None; Yan Wang, None; Melinda Duncan, None
  • Footnotes
    Support  5R01EY028597-03
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2100. doi:
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    • Get Citation

      Adam Faranda, Mahbubul H. Shihan, Yan Wang, Melinda K Duncan; The the Influence of Sex on the Aging Lens Transcriptome. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2100.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : Age is a major risk factor for cataract. However, the influence of aging on the lens transcriptome is under studied. While age related cataract affects both sexes, it is more prevalent in women than men. While estrogen withdrawal at menopause is implicated in this observation, how sex influences lens gene expression is unknown. Here, we elucidate the effect of sex and age on the lens transcriptome of inbred mice.

Methods : Lens epithelial (LEC) and fiber cells (LFC) were isolated from young (3 month) and aged (24 month) old C57Bl/6J mice of both sexes, RNA prepared, and subjected to RNAseq. EdgeR was used to estimate differential gene expression in pairwise contrasts, with Advaita’s Ipathway guide and custom R scripts to evaluate the biological significance of differentially expressed genes (DEGs).

Results : RNAseq revealed age dependent decreases in lens differentiation marker expression in both LECs and LFCs, with gamma crystallin transcripts downregulating nearly 50 fold in LFCs. Aged LECs upregulate genes controlling the immune response, complement pathways, and cellular stress responses, including glutathione peroxidase 3 (GPX3). Aged LFCs exhibit broad changes in the expression of genes regulating cell communication, and upregulate genes involved in antigen processing/presentation, cholesterol metabolism, and calcium signaling, while changes in the expression of mitochondrial respiratory chain genes are consistent with mitochondrial stress.
While young LECs only differentially express genes known to be associated with sex determination (i.e Xist in females, and Ddx3y in males), female LECs do not reduce crystallin transcription with age to the same extent as males nor do they upregulate GPX3 expression as dramatically as males. In contrast, young LFCs from males and females differentially express nearly fifty genes, many of which remain differentially expressed in aged LFCs. Notably, female LFCs retain substantially greater gammaD crystallin expression with age compared to males while also exhibiting enhanced upregulation of NDufa4l2, which encodes an alternate electron transport chain protein and is a marker of mitochondrial stress.

Conclusions : Lens cells downregulate the expression of lens markers with age while upregulating markers of inflammation, complement pathways, and cellular stress. Sex does not have a large impact on the young LEC transcriptome, but it does have a modest influence on gene expression in the aging lens.

This is a 2021 ARVO Annual Meeting abstract.


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