EyeWorld Asia-Pacific September 2020 Issue

CORNEA EWAP SEPTEMBER 2020 41 A new study is being hailed as a breakthrough in Fuchs endothelial dystrophy research, providing explanations to several questions surrounding this potentially blinding disorder. 1 Why is the disease found in the central cornea primarily? As a clinician scientist, Ula Jurkunas, MD, said she has had the longstanding observation that Fuchs dystrophy develops in the center of the cornea and spreads to the periphery. “A lot of times, if you lift the eyelid of the patient, the upper cornea that is covered by the eyelid has no findings, but it is the area that is interpalpebral, meaning it is exposed to sunlight, [where you see guttae],” Dr. Jurkunas said. With these observations and findings from earlier studies showing the involvement of oxidative stress in Fuchs pathogenesis, Dr. Jurkunas and coinvestigators hypothesized that ultraviolet light was a physiological stressor involved in the mechanism of Fuchs. They developed a mouse model to test this hypothesis, shining varying doses of ultraviolet light into mouse eyes (non-irradiated eyes served as controls) and following up for several months. Researchers identified alterations in mouse corneal endothelial cell morphology, cell density, and “guttae-like lesions” in irradiated eyes, which Dr. Jurkunas said were similar to those seen in human Fuchs patients. Why is it more common in women than men? Fuchs is known to have a genetic component, but women also seem to get it more than men, Dr. Jurkunas said. When studying their mouse model, Dr. Jurkunas said they unexpectedly saw significantly more female mice with endothelial cell changes after UV light exposure. “They developed Fuchs earlier and in a more severe form,” Dr. Jurkunas said. The researchers studied the effect of UV-A light on human corneal cells in vitro and identified a pathway that showed increased expression of the enzyme CYP1B1. This enzyme is involved in an estrogen metabolite pathway that leads to DNA damage. “I think men and women have this enzyme, but it is probably the tissues are more estrogen rich in females and that enzyme is expressed at higher levels in female tissues. However, it is present in men, and probably the people who do develop this, even men, have activation of this enzyme,” Dr. Jurkunas said. Is there a therapeutic pharmaceutical target? From there the researchers wondered about reversing the effects of this oxidative stress. N-acetylcysteine is well known in the scientific literature as a vast antioxidant, Dr. Jurkunas said. In ophthalmology, it’s Breakthrough in Fuchs research by Liz Hillman Editorial Co-Director Contact information Jurkunas: Ula_Jurkunas@meei.harvard.edu This article originally appeared in the June/July 2020 issue of EyeWorld . It has been slightly modified and appears here with permission from the ASCRS Ophthalmic Services Corp. Retroillumination image showing that Fuchs dystrophy affects central cornea, sparing the periphery or areas covered by the eyelids. Source: Ula Jurkunas, MD