# The Roles of Autophagy in Limbal/Corneal Epithelia.

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $480,797

## Abstract

PROJECT SUMMARY/ABSTRACT
The anterior surface of the eye functions as a barrier to the external environment, protects the delicate
underlying structures from injury, supports a tear film and maintains transparency. These functions are
achieved, in part, through the corneal and limbal epithelia, which must maintain proper proliferation and
differentiation. Autophagy, a catabolic process by which cells adapt to intrinsic and extrinsic stress-related
situations, has been shown to also regulate proliferation and differentiation. Despite the many advances made
in our understanding of corneal and limbal epithelial biology, autophagy remains largely unstudied. We have
recently reported that: (i) under resting conditions, autophagy is greater in limbal epithelial basal compared with
corneal epithelial basal cells; (ii) autophagy contributes to limbal epithelial proliferative capacity; and (iii)
autophagy enables proper activation of transit amplifying (TA) cells following wounding. We also have
preliminary evidence that: (i) NUS1 is a novel upstream regulator of autophagy in the limbal epithelium; (ii)
blocking autophagy impairs corneal epithelial differentiation and the removal of nuclear material (nucelophagy);
and (iii) the receptor tyrosine kinase, EphA2, positively affects corneal epithelial differentiation via regulating
end stage autophagy. These observations lead us to hypothesize that autophagy is required to maintain limbal
epithelial stem and TA cell homeostasis as well as insure proper corneal epithelial differentiation. We propose
to test this hypothesis by focusing on how autophagy: (i) affects limbal epithelial stem cell proliferation; (ii)
regulates differentiation in the corneal epithelium; and (iii) is regulated by EphA2 in the corneal epithelium. To
accomplish these goals, we will capitalize on our ability to conduct gain- and loss-of-function studies of
autophagy-related genes and their key up-stream regulators in complimentary model systems that include
cultured human limbal (HLEKs) and corneal (HCEKs) epithelial cells, 3-D raft cultures of limbal and corneal
epithelia, and mouse models of impaired autophagy and EphA2 signaling. We will assess the functional
consequences of such modulations with a combination of morphogenetic (including Structured Illumination
Microscopy and TEM), biochemical, molecular biological, cell biological and physiological approaches. By
focusing on autophagy, our proposal represents a new approach to study the regulation of: (i) limbal stem and
TA cell proliferation; and (ii) corneal epithelial differentiation and nucelophagy. Such knowledge has clinical
applicability as sustaining proliferation is necessary for the proper expansion of cultured HLEKs used in ex vivo
transplantation as well as in wound healing. The impact of autophagy and nucleophagy on corneal epithelial
differentiation has translational relevance since aberrant differentiation is a feature of diseases of the corneal
epithelium (e.g., aniri...

## Key facts

- **NIH application ID:** 10400950
- **Project number:** 5R01EY028560-05
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** ROBERT M LAVKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $480,797
- **Award type:** 5
- **Project period:** 2018-05-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10400950

## Citation

> US National Institutes of Health, RePORTER application 10400950, The Roles of Autophagy in Limbal/Corneal Epithelia. (5R01EY028560-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10400950. Licensed CC0.

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