# Hypoxia Regulation of the Lens

> **NIH NIH R01** · FLORIDA ATLANTIC UNIVERSITY · 2020 · $332,763

## Abstract

Project Summary/Abstract
This application seeks to identify novel mechanisms and regulatory pathways required to achieve the structure
and function of the eye lens. The lens consists of a surface layer of epithelial cells that during embryogenesis,
and throughout life, differentiate into lens fiber cells that make up the core and bulk of the lens. To achieve
their mature structure and transparent function, newly-formed lens fiber cells must complete a sequential
program of cellular remodeling hallmarked by the complete elimination of cellular organelles and the tightly
controlled expression of specialized lens proteins. Disruption of the lens fiber cell remodeling program causes
defective lens structure and cataract formation so that identification of these mechanisms and regulatory
pathways is critical for advancing our understanding of mature lens formation and pathology. We have recently
discovered that a key regulator of mitochondrial degradation in erythrocytes, called BNIP3L, is required for the
specific elimination of mitochondria, endoplasmic reticulum and Golgi apparatus in the embryonic lens during
formation of the lens organelle-free zone. These studies identify the first requirement for the elimination of non-
nuclear organelles during the remodeling of embryonic lens fiber cells and they establish an entirely novel
function for BNIP3L in the degradation of endoplasmic reticulum and Golgi apparatus. Experiments proposed
in AIM1 now seek to advance these findings by establishing a novel requirement for BNIP3L in the elimination
of these organelles during the remodeling of adult lens fiber cells and they seek to reveal the mechanisms,
regulatory pathways and auxiliary proteins required for their BNIP3L-dependent elimination. Lacking a blood
supply the lens contains a diminishing oxygen gradient from the lens surface to the lens core. Experiments AIM
2 are designed to test the novel hypothesis that lens hypoxia is a novel requirement for lens structure and
transparency through the hypoxia-dependent control of organelle-elimination in lens fiber cells and the
regulation of critical genes including BNIP3L, the cell-cycle exit protein p27 and the structural protein CP49,
through activation of the master regulator of the hypoxic response, hypoxia-inducible transcription factor
HIF1a. The successful completion of these AIMs will have a significant long-term impact on our understanding
of the cellular remodeling pathways leading the mature structure and transparent function of the eye lens. The
results are also expected to advance the identification of cellular remodeling pathways required for the
formation and function of more complex tissues.

## Key facts

- **NIH application ID:** 9986807
- **Project number:** 5R01EY029708-02
- **Recipient organization:** FLORIDA ATLANTIC UNIVERSITY
- **Principal Investigator:** Marc Kantorow
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $332,763
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986807

## Citation

> US National Institutes of Health, RePORTER application 9986807, Hypoxia Regulation of the Lens (5R01EY029708-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9986807. Licensed CC0.

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