# The Role of Aquaporins in Lens Structure and Function

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2024 · $423,753

## Abstract

The human lens must maintain transparency over many decades and, to do so without a blood supply, the lens
maintains a fluid microcirculation system (MCS) to deliver nutrients throughout the tissue. Although the influx of
water, ions, and nutrients occurs at the anterior and posterior poles via the lens sutures and fluid outflow occurs
toward the equatorial efflux zone, the molecular details of how the MCS is established and maintained with age
are not well understood. It is, however, agreed that spatial differences in the expression and functionality of
channels and transporters are critical to the generation of ion and fluid circulation. In this application we focus
on lens aquaporins (AQPs) that we hypothesize play important roles in generating the lens MCS by establishing
differences in water permeability in influx, outflow, and efflux zones. Aquaporin-0 (AQP0), the most abundant
lens membrane protein, has reported roles in lens fiber cell adhesion, in basal water permeability, and in fiber
cell organization and, as such, is vital for the development and maintenance of lens transparency. A second
aquaporin, AQP5, is also present in lens fiber cells and can act as a regulated water channel since mechanical
tension can alter AQP5 subcellular localization in fiber cells of the anterior pole and equator to presumably
dynamically regulate water permeability. The long-term goal of our research is to understand how lens protein
modifications that occur during development, aging, and cataractogenesis help establish or alter the MCS
thereby leading to lens transparency or opacification. In the context of the microcirculation system, we
hypothesize that AQP posttranslational modifications and AQP-lipid interactions are important molecular
mechanisms used to modulate AQP functionality in the influx, outflow, and efflux zones. To test our hypotheses,
we will employ advanced quantitative proteomics, native mass spectrometry, multi-modal imaging methods, and
water permeability assays to obtain a molecular level understanding of how the structures and functions of lens
AQPs change in influx, outflow, and efflux zones. Further, we will examine changes in AQP modifications and
subcellular localization in organ cultured lenses exposed to stimuli that either dynamically regulate lens water
transport or compromise the ability of the MCS to maintain lens transparency. This suite of methods will be
applied to lens to test three hypotheses: 1) that water influx into the lens is increased by AQP5 membrane
trafficking in the anterior suture region of the lens, 2) that AQPs direct intracellular water flow toward the lens
equator in the outflow zone, and 3) that AQP5 trafficking to the membrane in the efflux zone dynamically
regulates the MCS in response to mechanical tension, and oxidative or osmotic stress; stresses that mimic age
related nuclear and diabetic cataract, respectively. We expect to provide a new mechanistic understanding of
the roles of AQPs and their m...

## Key facts

- **NIH application ID:** 10796924
- **Project number:** 5R01EY013462-22
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Kevin L Schey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $423,753
- **Award type:** 5
- **Project period:** 2001-05-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10796924

## Citation

> US National Institutes of Health, RePORTER application 10796924, The Role of Aquaporins in Lens Structure and Function (5R01EY013462-22). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10796924. Licensed CC0.

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