image: Figure 11. A summary of the localization and protein levels of canonically active EphA2-pY589 and non-canonically active EphA2-pS898 in control and ephrin-A5-/- lenses from 6-week-old, 4-month-old, and 8-month-old mice. Canonical ligand-mediated EphA2-pY589 is only found in lens epithelial cells, and protein levels do not change with age. Non-canonical ligand-independent activation of EphA2-pS898 is found in epithelial cells and mature fiber cells in the lens cortex. The levels of EphA2-pS898 increase with age, and in ephrin-A5-/- epithelial cells, there is an increase compared to the control in 8-month-old mice. Cartoon not drawn to scale. Modified from [38].
Credit: 2024 Horner et al.
“Erythropoietin-producing hepatocellular carcinoma (Eph) receptors make up the largest family of human receptor tyrosine kinases (RTKs).”
BUFFALO, NY- November 13, 2024 – A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science), on October 25, 2024, Volume 16, Issue 20, titled, ”Canonical ligand-dependent and non-canonical ligand-independent EphA2 signaling in the eye lens of wild-type, knockout, and aging mice.“
Researchers from the School of Optometry and Vision Science Program at Indiana University have uncovered important new insights into how the aging affects the eye lens and contributes to cataract formation, a condition impacting millions worldwide. This study focuses on the EphA2 protein, traditionally associated with cancer, which researchers have now identified as essential for maintaining the lens’s clarity and function as it ages.
Cataracts are the leading cause of blindness worldwide, primarily affecting older adults, yet the precise biological mechanisms behind their formation remain unclear. This research sheds light on the role of the EphA2 protein receptor in the eye lens, revealing that it operates through two distinct signaling pathways: a canonical (ligand-dependent) and a non-canonical (ligand-independent) pathway. By studying various groups of mice, including those lacking the EphA2 protein receptor and its ligand partner ephrin-A5, scientists observed how these signaling pathways change with age, affecting the organization and maturation of lens cells.
Researchers Jenna L. Horner, Michael P. Vu, Jackson T. Clark, Isaiah J. Innis, and Catherine Cheng observed that EphA2’s canonical signaling, which organizes lens cells, remains stable in aging lens tissue, particularly in epithelial cells. They found that the non-canonical signaling pathway—previously associated primarily with aggressive cancer cells—increases with age in normal lens cells. This increase suggests that non-canonical signaling plays a crucial role in helping lens fiber cells mature and maintain their structure over time.
“Here, we report that canonical ligand-mediated EphA2 activation is restricted to the lens epithelial cells and show the first evidence of physiological non-canonical EphA2 activity in a normal tissue.”
This understanding could lead to new therapies targeting EphA2 to delay or prevent cataracts.
In conclusion, this study represents a significant advance in understanding the cellular mechanisms behind lens aging and cataract development, potentially paving the way for new non-surgical cataract treatments.
Read the full paper: DOI: https://doi.org/10.18632/aging.206144
Corresponding author: Catherine Cheng - ckcheng@iu.edu
Keywords: aging, fiber cells, epithelial cells, Y588, Y589, S897, phosphorylation, maturation, ephrin
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About Aging:
The journal Aging aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)
Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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Journal
Aging-US
Method of Research
News article
Subject of Research
Animals
Article Title
Canonical ligand-dependent and non-canonical ligand-independent EphA2 signaling in the eye lens of wild-type, knockout, and aging mice
Article Publication Date
25-Oct-2024
COI Statement
The authors report no conflict of interest.