2022 Annual Meeting and Alumni Reunion
Category : Basic and Translational Research Candidate : Francesca Kahale Poster #: B12
Cyto-protective Effect of Alpha-Melanocyte-Stimulating Hormone on UV-A Induced Fuchs Endothelial Corneal Dystrophy
Francesca Kahale ; Neha Deshpande ; Hamid Alemi ; Amir Reza Naderi , Shudan Wang ; Tomas Blanco ; Thomas H Dohlman ; Jia Yin ; Ula V Jurkunas ; Reza Dana
Purpose : Fuchs Endothelial Corneal Dystrophy ( FECD ) is characterized by a progressive loss of corneal endothelial cells ( CEnC ) from accumulated exposure to oxidative stress . FECD is a leading cause of corneal transplantation worldwide with no definitive pharmacologic treatment available . UV radiation , specifically UV-A has been shown to induce DNA damage by means of free radical generation , contributing to FECD pathogenesis . We have previously demonstrated the protective function of the neuropeptide alpha-Melanocyte Stimulating Hormone ( α-MSH ) against oxidative stress on ex vivo corneas . This study aims to investigate the in vivo protective effect of α-MSH in a mouse model of UV-A irradiation ind
Methods : 8-week-old female C57BL / 6 mice ( n = 6 / group ) were irradiated with UV-A for 16 minutes , delivering a dose of 500J / cm2 . Mice received an intraperitoneal injection of 0.01mL / g of α-MSH ( 10-4 M ) immediately following irradiation and thrice weekly for 4 weeks . CEnC density , hexagonality , and coefficient of variation ( CV ) were evaluated by in vivo confocal microscopy pre-irradiation and at day 1 , 14 and 28 post-irradiation . Image analysis was done via the KONAN CellChek ® software . Corneal edema was evaluated by measuring central corneal thickness by optical coherence tomography .
Results : Corneal endothelial cells visualized by in vivo confocal microscopy pre-UV exposure at days 14 and 28 . At day 28 , mean cell density was significantly higher in the treated ( 1970.9 ± 285 cells / mm2 ) compared to the untreated group ( 1137.5 ± 398 cells / mm2 ), p = 0.0005 . Polymegathism evaluated by coefficient of variation was also significantly lower in the treated group at 37.2 ± 5.5 compared to untreated at 64.4 + 20.3 ( p = 0.005 ). Percentage of cells retaining hexagonality was significantly higher in the treatment group ( 54.3 ± 3.4 %) compared to untreated ( 45.1 ± 6.8 %), p = 0.006 . Central corneal thickness measured by optical coherence tomography demonstrates difference in CCT starting at D14 between treated and untreated groups . By day 28 , corneal edema is significantly higher in the untreated group ( 114.8 ± 16.5μm ) compared to treated group ( 93.4 ± 5.4μm ), p = 0.0074 .
Conclusions : Treatment with α-MSH leads to a decrease in UV-A induced CEnC cell loss and preserves cellular morphology . The conferred endothelial cyto-protection prevents corneal decompensation and edema .