# Characterization of Corneal Defects in ATG7-Deficient Mice

## TL;DR

This study shows that ATG7 is crucial for corneal health, and its absence leads to epithelial thickening and increased lymphatic vessels, suggesting a role in eye surface diseases.

## Contribution

The study reveals novel compensatory pathways in ATG7-deficient corneal epithelium and their implications for immune privilege and lymphangiogenesis.

## Key findings

- ATG7 deficiency disrupts autophagosome formation and leads to epithelial thickening and lymphatic vessel sprouting.
- Proteomic analysis shows upregulation of RAB8, TM9S3, and RETR3, indicating compensatory exophagy, reticulophagy, and Golgiphagy.
- Downregulation of inflammatory and angiogenic components suggests a moderate loss of inhibitory capacity in ATG7-deficient corneas.

## Abstract

Regulated proteolysis via autophagy is essential for cellular homeostasis, yet the specific role of autophagy-related gene 7 (ATG7) in corneal epithelial maintenance remains unclear. Using a conditional knockout mouse model (Atg7f/f K14Cre+/−), we investigated the impact of ATG7 deficiency on corneal epithelial autophagy, morphology, and vascular dynamics. Loss of ATG7 disrupted autophagosome formation, evidenced by increased LC3B expression but reduced LC3B-positive puncta and absence of autophagosomes ultrastructurally. Although gross corneal morphology was preserved, ATG7 deficiency led to thickened epithelium and increased peripheral lymphatic vessel sprouting, indicating a pro-inflammatory and pro-lymphangiogenic microenvironment. Proteomic analysis revealed upregulation of RAB8, TM9S3, and RETR3, suggesting activation of compensatory pathways such as exophagy, reticulophagy, and Golgiphagy. Inflammatory and angiogenic components were downregulated, suggesting a moderate loss of inhibitory capacity based on the lymphatic phenotypes observed. At the same time, while these two compensatory changes occur, other proteins that positively regulate lysosome formation are reduced, resulting in a phenotype linked to deficient autophagy. These findings demonstrate that ATG7-mediated autophagy maintains corneal epithelial homeostasis and immune privilege, with implications for understanding corneal inflammation and lymphangiogenesis in ocular surface diseases.