UBIAD1 and ferroptosis: exploring a cure for Schnyder Corneal Dystrophy (SCD)

A genetic disorder is an illness caused by abnormalities in genes or chromosomes. Most genetic
disorders are quite rare and affect one in every several thousands or millions of people. There are many diseases that can be treated with pharmacological, gene, or cellular therapy. Our lab is working on a genetic disease called Schnyder Corneal Dystrophy (SCD). SCD is an autosomal dominant genetic disease characterized by progressive opacification of the cornea as a result of abnormal deposits of free cholesterol and phospholipids. Corneal opacification leads to gradual decrease of visual activity and blindness. At this moment no treatment is available to stop its progression. Phototherapeutic keratectomy can remove subepithelial crystals that affect visual acuity. Penetrating keratoplasty can be performed in eyes with advanced disease but can recur in the graft. Recently, SCD has been associated with mutations in the human UBIAD1 gene on chromosome 1p36. The function of Ubiad1 protein is still far from being completely understood.  Our aim is to explain how UBIAD1 mutations leads to the pathogenesis of the Schnyder Corneal Dystrophy as it characterizes its function and to propose new specific therapies. Our analyses will be carried out in the context of whole organism models and human primary corneal stem cells. The aim is to provide a new hypothesis about disease−gene function, and provide new insights for new therapeutic approaches in the cure of SCD patients.