# Regulation of pHi and Fluid Flux in Corneal Endothelium

> **NIH NIH R01** · TRUSTEES OF INDIANA UNIVERSITY · 2020 · $425,273

## Abstract

There are three major goals of this project period: 1) to demonstrate that the corneal endothelial
PUMP is based on Lactate-Water coupled transport, 2) to determine the detailed physiological
mechanism for the Lactate-Water coupled system, and 3) to begin to use this basic science
knowledge to reverse corneal edema in Endothelial Dystrophy. The PUMP maintains corneal
hydration and transparency. When the PUMP fails due to trauma, inflammation, ageing, or
corneal dystrophy, corneal edema ensues, transparency is lost and vision is significantly
degraded. The usual therapy is transplantation, which is not without significant compromises
and complications. Knowing how the PUMP works is one approach to developing medical
therapies that could delay or supplant the need for transplantation. Ion transport is a key feature
of the PUMP. Over the previous 5-7 years we have provided strong evidence that the PUMP
works by transporting lactate ions from the stroma to the anterior chamber. This lactate flux is
facilitated by cellular and aqueous humor buffering power from CO2/HCO3- and the carbonic
anhydrase system. Our data indicate that water flux is directly linked with lactate flux. We
hypothesize that the endothelial cells create a standing [lactate] gradient that drives water
osmotically from the stroma to the anterior chamber. Secondly, we show that lactate transport is
compromised in a model of endothelial dystrophy. Therefore, we propose that enhancing lactate
flux can reduce corneal edema in endothelial dystrophies. Using multiple in vitro, in vivo & ex
vivo complementary approaches this will be tested in three aims. Aim #1 will provide
experimental conditions that fill gaps in the evidence so that we can confirm the hypothesis that
lactate flux, facilitated by active transport mechanisms, is the major contributor to the corneal
endothelial PUMP. Aim 2 will determine the mechanism for coupling fluid flux to lactate flux by
testing the hypothesis that a transendothelial [lactate] standing-gradient is present and examine
the alternate hypothesis that water flux is linked directly to monocarboxylate cotransporter
(MCT) flux. Aim 3 will test the hypothesis that Endothelial PUMP function, in normal and
distressed cells, can be enhanced via Hypoxia Adaptation. If this hypothesis is correct, it will
have the potential to be tested as a therapy for Fuchs Dystrophy.

## Key facts

- **NIH application ID:** 9893877
- **Project number:** 5R01EY008834-29
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** Joseph Aurelio Bonanno
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $425,273
- **Award type:** 5
- **Project period:** 1991-07-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893877

## Citation

> US National Institutes of Health, RePORTER application 9893877, Regulation of pHi and Fluid Flux in Corneal Endothelium (5R01EY008834-29). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9893877. Licensed CC0.

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