# Modeling and testing functional interactions among corneal endothelial acid-base transporters

> **NIH NIH R21** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2024 · $245,647

## Abstract

In a healthy cornea, optimal corneal hydration and transparency is maintained by the corneal
endothelial cells that pump fluid out of the stroma. The pump requires the action of three stromal-
facing transport proteins: the Na+/CO3= cotransporter NBCe1 and the H+/Lactate- transporter
MCT1. However, it is unclear why mutations in another protein, the pH-dependent H+ conductor
SLC4A11, cause loss of pump function and thence corneal dystrophy. We hypothesize that
SLC4A11 supports the activity of the pump by counteracting pH changes that result from
imbalances in NBCe1 and MCT1 action. Understanding the complex functional interactions
among these three acid-base transporters with co-expression studies only is virtually impossible
because intuition alone is not sufficient for data interpretation. Mathematical models, developed
in conjunction with experimental approaches, provide a powerful tool to overcome this difficulty.
Thus, here we propose to use experimental data gathered from Xenopus oocytes expressing
these transporters singly, in pairs, or as a trio, in combination with kinetic parameters that have
been determined for each transporter, to generate a computational model that mimics our in vitro
experiments. This multidisciplinary approach will allow us quantify the power of SLC4A11 to
prevent pH change during imbalanced NBCe1/MCT1 action, disclose synergistic and antagonistic
interactions among the three, and predict the effects of disease-causing mutations that shift the
abundance and/or pH dependence of SLC4A11 on intracellular pH balance and on the ion fluxes
that support pump function.

## Key facts

- **NIH application ID:** 10869464
- **Project number:** 1R21EY036218-01
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Rossana Occhipinti
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $245,647
- **Award type:** 1
- **Project period:** 2024-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10869464

## Citation

> US National Institutes of Health, RePORTER application 10869464, Modeling and testing functional interactions among corneal endothelial acid-base transporters (1R21EY036218-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10869464. Licensed CC0.

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