June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
The adult human lens transcriptome changes with age
Author Affiliations & Notes
  • Melinda K Duncan
    Biological Sciences, University of Delaware, Newark, Delaware, United States
  • Adam Faranda
    Biological Sciences, University of Delaware, Newark, Delaware, United States
  • Samuel G Novo
    Biological Sciences, University of Delaware, Newark, Delaware, United States
  • Justin d'Antin
    Centre d'Oftalmologia Barraquer, Barcelona, Catalunya, Spain
  • Yan Wang
    Biological Sciences, University of Delaware, Newark, Delaware, United States
  • Mahbubul H Shihan
    Biological Sciences, University of Delaware, Newark, Delaware, United States
  • Footnotes
    Commercial Relationships   Melinda Duncan Pliantx, Code C (Consultant/Contractor); Adam Faranda None; Samuel Novo None; Justin d'Antin None; Yan Wang None; Mahbubul Shihan None
  • Footnotes
    Support  EY028597
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 3105. doi:
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      Melinda K Duncan, Adam Faranda, Samuel G Novo, Justin d'Antin, Yan Wang, Mahbubul H Shihan; The adult human lens transcriptome changes with age. Invest. Ophthalmol. Vis. Sci. 2022;63(7):3105.

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

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Abstract

Purpose : Aging is a major risk factor for cataract due to a combination of factors including age-related protein and lipid oxidation/damage, reduction in the ability of the lens to detoxify reactive oxygen species, and genetic alterations that could disrupt cellular structure. However, most tissues also alter gene expression with age even in the absence of pathology, and we found that the transcriptome of the aging mouse lens does as well, predicting pathways that could be either protective against cataract development or may exacerbate age-related declines in lens transparency. However, lab mice have a much shorter life span than humans thus the relationship between lens aging in mouse and human is unclear. This work seeks to fill this knowledge gap by investigating the transcriptomic changes of the aging human lens.

Methods : Young (20-30 years of age) and aged (70-89 years of age) human lenses were isolated from human cadavers during preservation of corneas for transplant by eye banks and immediately immersed in RNAlater prior to shipment to our laboratory. The lenses were dissected into central epithelium, equatorial epithelium, and cortical fibers, and total RNA prepared. RNA was converted to cDNA then sequencing libraries prepared using SMARTer Stranded Total RNA-Seq Kit-Pico kit and double strand sequenced by DNA Link. Read pairs were mapped to the human genome, data normalized and differential expression assessed using EdgeR. Differential expressed genes were mapped to pathways via iPathway Guide.

Results : Principal component analysis revealed that cell type (central epithelium, equatorial epithelium versus fibers) was the strongest factor driving lens gene expression, while age only accounted for 12% of the variance between samples. Aged lens fibers downregulate the expression of several hundred genes including the BMP regulator Crim1, numerous lens fiber cell markers and several enzymes responsible for glutathione metabolism, while less than 100 genes were upregulated with aging. Central and equatorial epithelial samples exhibit fewer gene expression changes with aging, while GSTM1 is the most downregulated gene in both cell types. Aged equatorial epithelium downregulates the expression of many lens marker genes consistent with the results in the cortical lens fibers.

Conclusions : Human lenses, like those of mice, differentially express numerous genes during aging, including many enzymes involved in glutathione metabolism.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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