# Permeability of Lens Gap Junction Channels

> **NIH NIH R01** · STATE COLLEGE OF OPTOMETRY · 2021 · $337,875

## Abstract

PROJECT SUMMARY
 Intercellular communication mediated by Cx46 and Cx50 gap junction channels is
central to the transport of ions into the lens and to the maintenance of lens transparency.
Studies on KO mice and on Cx46 and Cx50 mutations have established that the absence of gap
junctional coupling leads to cataracts. The main focus of this proposal is to examine the role of
gap junction (GJ) channels in the development of age-related nuclear cataracts. A key factor
that influences nuclear cataract formation is the abrupt age-dependent decline in the levels of
reduced glutathione (GSH) in the lens nucleus. This reduction in GSH levels is not observed in
the outer cortex and therefore has been attributed to the formation of a barrier to the diffusion of
GSH that develops with age. We have used electrophysiological techniques to show that that
Cx46 and Cx50 channels are permeable to GSH. Additional studies indicated that GSH is likely
to diffuse via Cx46 GJs from the cells in the outer cortex, where the anti-oxidant is synthesized,
to the metabolically quiescent cells in the lens nucleus. In this proposal, we will examine the role
of GJ channels in: (1) the establishment of a reducing environment in the lens nucleus, and (2)
mediating the shift to an oxidized environment that occurs with aging. We will use imaging and
mass spectrometry methods to directly measure the variation in the glutathione redox potential
from the lens periphery to the center in the intact lens. In Aim 1, we will assess the influence of
coupling levels on the spatial profile of glutathione redox potential in the intact lens. In Aim 2, we
will determine the permeability of gap junctions to other metabolites known to be essential for
the overall redox state of cells deep in the lens. In Aim 3, we will examine the relationship
between GJ channel functionality and changes in the glutathione redox potential that occur with
age. Specifically, we will determine whether post-translational modifications to Cx46 and Cx50
accumulate with age, leading to a reduction in GJ coupling, and ultimately to the development of
the barrier to GSH diffusion. These studies thus make a direct contribution to the understanding
of the mechanisms underlying the formation of ARN cataracts, and will serve to further highlight
the key role of GJ channels in maintenance of lens transparency.

## Key facts

- **NIH application ID:** 10200058
- **Project number:** 5R01EY028170-05
- **Recipient organization:** STATE COLLEGE OF OPTOMETRY
- **Principal Investigator:** Miduturu Srinivas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $337,875
- **Award type:** 5
- **Project period:** 2017-08-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200058

## Citation

> US National Institutes of Health, RePORTER application 10200058, Permeability of Lens Gap Junction Channels (5R01EY028170-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10200058. Licensed CC0.

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