Hadrian, Karina - assoc. RG

Congenital aniridia is a rare, panocular disease primarily caused by heterozygous PAX6 mutations, leading to severe ocular malformations and progressive vision loss. As PAX6 orchestrates key developmental pathways, its haploinsufficiency disrupts the formation of various ocular structures including the iris, fovea, and cornea, often resulting in secondary complications such as keratopathy, glaucoma, and cataract. In particular, aniridia-associated keratopathy (AAK) compromises the immune-privileged, avascular cornea, severely limiting visual acuity and complicating surgical outcomes. Corneal transplantation, treatment for advanced AAK, shows poor prognosis in pre-vascularized, inflamed beds typical of aniridia patients. Our research focuses on the Aey80 Pax6 mutant mouse model, which exhibits hallmark features of human aniridia, including iris hypoplasia, corneal thickening, edema, and pathological vascularization. We aim to (i) characterize age-related immunological and morphological changes in the cornea and periocular glands, (ii) assess inflammatory and angiogenic responses to injury and treatment, and (iii) develop a high-risk corneal transplantation model in PAX6-deficient mice. Using transcriptomic profiling, flow cytometry, and functional lacrimal gland assays, we will map disease mechanisms and test (established) therapeutic interventions - such as aflibercept, NFAT5 modulation, and sCD83 treatment - to improve graft survival and identify novel therapeutic strategies.

This study supports sustainable advances in rare eye disease by characterizing aniridia through a validated model and evaluating clinically relevant interventions. Translationally, it enables the refinement of high-risk corneal transplantation and fosters targeted, non-surgical therapies, promoting long-term vision preservation and reducing reliance on scarce donor tissue.

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• Center for Molecular Medicine Cologne (CMMC)
• Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany
• FOR 2240: (Lymph)angiogenesis and cellular immunity in inflammatory diseases of the eye
• CRC 1607