# Intercellular Communication in the Eye Lens

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2020 · $343,125

## Abstract

Project Summary
 Lens, an avascular organ, relies heavily on a network of transporting systems to deliver nutrients and other
essential components to bulky lens fibers and excrete wastes. Differentiated nuclear fiber cells never turn over
and oxidative stress is a major cause of age related cataracts. Connexin (Cx)-forming gap junction channels
play an essential role for the metabolic homeostasis of the lens. Besides gap junctions, connexins form
hemichannels, permitting transport of molecules between the cell and its extracellular environment. Connexins
are truncated in nuclear fibers and this cleavage is increased with aging and oxidative stress. However, little is
known regarding the functional importance and regulation of hemichannels formed by full-length and truncated
connexins in lens fibers. Our preliminary studies indicate that hemichannels in cortical lens fibers are activated
by mechanical loading, mediate uptake of glucose and glutathione, and exhibit self-protective roles againist
oxidative damages. As such, we hypothesize that (1) The hemichannels formed by Cx50/Cx46 are activated
by mechanical stimulation in cortical lens fibers and mediate uptake of nutrients/antioxidants, which are
delivered to inner cortical and nuclear fibers via gap junctions to maintain cell homeostasis and viability; (2)
Functional hemichannels formed by both full length and truncated Cx50/Cx46 exhibit self-protection against
oxidative damages. The goal is to understand distinctive, new roles of connexin hemichannels in lens fiber
cells under normal physiological and pathological (e.g. oxidative stress) conditions. In this proposal, first, we
will determine if connexin hemichannels activated by mechanical loading serve as a major transport pathway
facilitating the uptake of nutrients and antioxidants into cortical lens fibers, and the role of integrins in regulating
hemichannels. Second, we will test if nutrients/antioxidants uptaken by hemichannels in cortical fibers are
delivered through gap junctions to inner cortical and nuclear fibers to meet metabolic needs of cell
homeostasis and protect inner fiber cells. Third, we will determine if hemichannels formed by both full-length
and truncated Cx50/Cx46 offer a self-protective mechanism against oxidative insult. One of the major
innovative aspects is that this proposal aims to uncover a novel role that connexin hemichannels formed by
full-length and truncated connexins play in facilitating metabolic function of lens fibers and protecting fiber cells
against oxidative damages. We will use established lens primary cultures and retroviral expression in lens in
situ, a newly developed dominant negative ex vivo approach, and knockout mouse models. It is our
expectation that elucidation of mechanistic roles of connexin channels in lens fibers will provide a better
understanding of the general homeostatic process of lens under normal and pathological conditions. The
outcomes of our research will be significant beca...

## Key facts

- **NIH application ID:** 9878855
- **Project number:** 5R01EY012085-22
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Jean X Jiang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $343,125
- **Award type:** 5
- **Project period:** 1998-02-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878855

## Citation

> US National Institutes of Health, RePORTER application 9878855, Intercellular Communication in the Eye Lens (5R01EY012085-22). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9878855. Licensed CC0.

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