Project: SUF

This funded pilot project investigates the role of the Aryl Hydrocarbon Receptor (AhR) in corneal tissue and explores its therapeutic potential in corneal neovascularization and transplant rejection. AhR is a ubiquitously expressed cytosolic transcription factor that responds to environmental, physiological, and xenobiotic ligands and regulates a broad spectrum of inflammatory, immune-related, and metabolic pathways. Beyond its classical role in activating xenobiotic response enzymes such as CYP1A1, CYP1A2, and CYP1B1, AhR signaling has emerged as an important regulator of immune homeostasis and tissue inflammation.

Recent studies have highlighted the relevance of AhR signaling in inflammatory and degenerative diseases of barrier tissues, including the skin and the eye. The first-in-class AhR ligand Tapinarof, already approved for inflammatory skin diseases, has demonstrated anti-inflammatory and immunomodulatory properties and may represent a promising therapeutic candidate for ocular surface diseases. Experimental evidence further suggests that AhR signaling influences corneal inflammation, endothelial dysfunction, fungal keratitis, and retinal pathology, although both protective and pro-angiogenic effects have been reported depending on the experimental context.

The central objective of this project is to characterize AhR-dependent signaling pathways in corneal epithelial cells and compare them with established epidermal keratinocyte models. Using human and murine epithelial cell lines, the project will investigate how distinct AhR ligands, environmental stressors such as UVA irradiation and hypoxia, microbial stimuli, and retinoids modulate inflammatory, immunosuppressive, and angiogenic pathways in barrier tissues. Particular focus will be placed on signaling molecules relevant to corneal immune regulation and pathological (lymph-)angiogenesis, including VEGF signaling, sCD83, ITGA5, IL-10, GM-CSF, VCAM1, and PD-L1.

In parallel, the project aims to establish immunohistochemical analyses of AhR and its downstream target CYP1A1 in human diseased corneal tissues to investigate the clinical relevance of AhR signaling in transplant-associated corneal pathology.

By integrating expertise in ocular surface biology, immunology, and barrier tissue research, this project establishes a novel interdisciplinary framework for understanding AhR-mediated immune regulation in the eye. The findings are expected to uncover mechanistic similarities and differences between skin and corneal epithelial biology and may identify AhR modulation as a potential therapeutic strategy for corneal inflammation, neovascularization, and transplant rejection.

Key Methods

• Corneal epithelial and keratinocyte cell culture models
• Treatment with AhR ligands including Tapinarof