# Mechanisms and consequences of impaired glutathione homeostasis in the aging lens

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2024 · $385,000

## Abstract

Abstract
 The integrity of the lipid and cholesterol-enriched lens membrane is vital to lens homeostasis, stiffness, and
transparency, serving as an impermeable barrier to cations and scaffold for major lens membrane proteins, such
as aquaporin 0 (AQP0) and ion pump. Aging is a primary risk factor for cataractogenesis and presbyopia, and it
drives a significant degree of lens membrane lipids compositional changes, such as the decline of unsaturated
glycerophospholipids and the steady increase of more saturated sphingomyelin lipids. The steep decline of highly
unsaturated glycerophospholipids in the lens is believed to result from selective lipid peroxidation, closely
associated with lens stiffness and membrane disintegration. Accumulated lens membrane disintegration can
cause a cataract, and increased lens stiffness is a primary cause of presbyopia. Despite overwhelming
suggestions, the direct link between lipid peroxidation and lens membrane transformation, and its impact on lens
stiffness and opacity, has yet to be established. Our studies have suggested that GPX4/GSH plays a crucial role
in maintaining lens plasma membrane integrity and transparency, as well as protecting against lipid peroxidation-
mediated cell death, such as ferroptosis. In this application, we aim to address these questions using in vitro
lens epithelial cell culture and in vivo mouse models directly targeting GPX4. The outcome of this study will
provide valuable insights into the lens membrane biology of aging and age-related cataractogenesis and
presbyopia.

## Key facts

- **NIH application ID:** 10801111
- **Project number:** 2R01EY028158-06
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Xingjun Fan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $385,000
- **Award type:** 2
- **Project period:** 2018-04-01 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801111

## Citation

> US National Institutes of Health, RePORTER application 10801111, Mechanisms and consequences of impaired glutathione homeostasis in the aging lens (2R01EY028158-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10801111. Licensed CC0.

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