Disease Pathogenesis

Disease pathogenesis
 

Researchers from Mass Eye and Ear, led by cornea specialist Dr. Ula V. Jurkunas, have significantly advanced our understanding of Fuchs dystrophy. Their findings include:
• Oxidative stress: Lifelong accumulation of oxidative damage leads to mitochondrial dysfunction and subsequent cell death of the corneal endothelium.
• Interaction between genetics and ultraviolet light exposure: Exposure to ultraviolet A light sets off an enzyme reaction that causes DNA damage in the corneal endothelial cells in patients with Fuchs dystrophy. This reaction is more pronounced in women as it is driven by the activation of CYP1B1, an enzyme that converts estrogen into metabolites that cause DNA damage. Patients with Fuchs dystrophy are now counseled on UV protection.
• Activation of endothelial-to-mesenchymal transition state: Diseased endothelial cornea cells undergo increased endothelial mesenchymal transition, which causes cellular senescence and leads to fibrosis and scarring in the form of guttae.

These findings have laid the groundwork for future corneal research and may facilitate the development of novel molecular targets for the disease.