| Autor: |
Ceravolo I; Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy., Mannino F; Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy., Irrera N; Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy., Minutoli L; Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy., Arcoraci V; Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy., Altavilla D; Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, Via C. Valeria, 98125 Messina, Italy., Cavallini GM; Institute of Ophthalmology, University of Modena and Reggio Emilia, Via del Pozzo, 41100 Modena, Italy., Guarini S; Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Via G. Campi, 41125 Modena, Italy., Squadrito F; Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy., Pallio G; Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy. |
| Abstrakt: |
Fuchs endothelial corneal dystrophy (FECD) is a bilateral, hereditary syndrome characterized by progressive irreversible injury in the corneal endothelium; it is the most frequent cause for corneal transplantation worldwide. Oxidative stress induces the apoptosis of corneal endothelial cells (CECs), and has a crucial function in FECD pathogenesis. The stimulation of the adenosine A 2A receptor (A 2Ar ) inhibits oxidative stress, reduces inflammation and modulates apoptosis. Polydeoxyribonucleotide (PDRN) is a registered drug that acts through adenosine A 2Ar . Thus, the goal of this study was to assess the effect of PDRN in an in vitro FECD model. Human Corneal Endothelial Cells (IHCE) were challenged with H 2 O 2 (200 μM) alone or in combination with PDRN (100 μg/mL), PDRN plus ZM241385 (1 μM) as an A 2Ar antagonist, and CGS21680 (1 μM) as a well-known A 2Ar agonist. H 2 O 2 reduced the cells' viability and increased the expression of the pro-inflammatory markers NF-κB, IL-6, IL-1β, and TNF-α; by contrast, it decreased the expression of the anti-inflammatory IL-10. Moreover, the pro-apoptotic genes Bax, Caspase-3 and Caspase-8 were concurrently upregulated with a decrease of Bcl-2 expression. PDRN and CGS21680 reverted the negative effects of H 2 O 2 . Co-incubation with ZM241385 abolished the effects of PDRN, indicating that A 2Ar is involved in the mode of action of PDRN. These data suggest that PDRN defends IHCE cells against H 2 O 2 -induced damage, potentially as a result of its antioxidant, anti-inflammatory and antiapoptotic properties, suggesting that PDRN could be used as an FECD therapy. |
