The limbal stem cell niche in development, insights from mouse models and children with aniridia

Abstract

Congenital aniridia, a rare eye disease of underdevelopment of the eye, leads to multiple eye abnormalities and pathologies, including a progressive limbal stem cell deficiency leading to the emergence and progression of an aniridia‐associated keratopathy. A deeper understanding of the characteristics of this deficiency could help to explain the observed pattern of progression and may provide insights into future treatments of this, and other types of limbal stem cell deficiency. From imaging studies in infants and young children with aniridia but with clear corneas, early phenotypic changes are apparent at the limbal border, with vascular tissue and inflammation apparent. In the central cornea, elevated inflammation and a nerve deficit are present early in life. In a novel mouse model of aniridia with slow development of keratopathy, limbal stem cell markers are perturbed after birth in clear corneas, and exhibit a characteristic time‐dependent pattern as the onset of clinically visible keratopathy emerges and starts to progress. Changes in the stromal and subbasal corneal nerves are also visible in the model and can provide insights into the neural deficit seen in the human disease. The model is moreover ideal for the evaluation of novel compounds aiming to slow the progression of keratopathy and preserve corneal transparency.