# Age related changes in lens transport and cataract

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2022 · $336,833

## Abstract

Project Summary/Abstract
The lens pathologies presbyopia and cataract are the leading causes of age related refractive error and vision
loss in the world today. The transparency and refractive properties of the lens are determined by its geometry
(shape and volume) and its inherent gradient of refractive index (water to protein ratio), which are in turn
maintained by the cellular physiology provided by the internal microcirculation system. This system utilizes
spatial differences in ion channels, transporters and gap junctions to establish standing electrochemical and
hydrostatic pressure gradients to drive the transport of ions, water and nutrients through the avascular lens. It
is our hypothesis that the process of aging has negative effects on lens transport, degrading ion and water
homeostasis, and producing changes in lens water content. This age-dependent decline in water transport
alters the optical properties of the lens, causing changes in optical quality and accommodative amplitude that
initially result in presbyopia in middle age and ultimately manifest as cataract that requires surgical correction
in the elderly. To test this hypothesis, we propose to identify additional components regulating water transport
activity in the intact mouse lens ex vivo. We will use impedance and intracellular hydrostatic pressure
measurements to monitor intracellular water transport in mice with pharmacological blockade or targeted
deletions of transport proteins. We will then use Magnetic Resonance Imaging (MRI) to spatially map the effect
changing mouse lens water transport has on total free water content, the water to protein ratio (refractive
index) and lens surface geometry. To investigate whether changes in lens water content are associated with
the onset and progression of human cataract, our recently developed in vivo MRI-based optical modelling
platform will be applied to patients who are scheduled to undergo vitrectomy and age matched control
subjects. Studying vitrectomy patients will allow changes in water transport preceding cataract formation to be
followed longitudinally in an accelerated time frame compared to normally ageing humans. To study the
relationship between lens geometry and water distribution during accommodation in the human lens in vivo, we
will use our MRI imaging protocols to monitor key parameters of lens transport non-invasively in volunteer
human subjects during accommodation. These proposed studies will use transgenic mouse models to gain
mechanistic insights into how lens water transport contributes to maintenance of the optical properties of the
lens, which will then be translated into human studies to assess how water transport contributes to the
development of presbyopia and the onset of nuclear cataract. Insights from these studies could potentially lead
to novel therapeutic interventions to alleviate the burden of the age-related lens pathologies.

## Key facts

- **NIH application ID:** 10475686
- **Project number:** 5R01EY026911-07
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** THOMAS W WHITE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $336,833
- **Award type:** 5
- **Project period:** 2016-08-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475686

## Citation

> US National Institutes of Health, RePORTER application 10475686, Age related changes in lens transport and cataract (5R01EY026911-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10475686. Licensed CC0.

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