Beneficial Effects of Polydeoxyribonucleotide (PDRN) in an In Vitro Model of Fuchs Endothelial Corneal Dystrophy

Abstract

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 A2A receptor (A2Ar) inhibits oxidative stress, reduces inflammation and modulates apoptosis. Polydeoxyribonucleotide (PDRN) is a registered drug that acts through adenosine A2Ar. 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 H2O2 (200 μM) alone or in combination with PDRN (100 μg/mL), PDRN plus ZM241385 (1 μM) as an A2Ar antagonist, and CGS21680 (1 μM) as a well-known A2Ar agonist. H2O2 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 H2O2. Co-incubation with ZM241385 abolished the effects of PDRN, indicating that A2Ar is involved in the mode of action of PDRN. These data suggest that PDRN defends IHCE cells against H2O2-induced damage, potentially as a result of its antioxidant, anti-inflammatory and antiapoptotic properties, suggesting that PDRN could be used as an FECD therapy.

Effect of Polydeoxyribonucleotide on Human Periodontal Ligament Cells as a Storage Medium for Avulsed Tooth

“…This finding is consistent with those of previous studies. In a study targeting human corneal endothelial cells, PDRN (100 μg/mL) significantly increased the survival rate of cells under oxidative stress [34]. In another in vitro study, PDRN significantly enhanced the proliferation of human skin fibroblasts in a concentration-dependent manner, and the effect was highest at a concentration of 100 μg/mL [35].…”

“…The findings of the current study suggest that PDRN inhibits the inflammatory response by reducing the expression levels of several inflammatory cytokines. In previous studies, PDRN has been reported to have antiinflammatory effects by reducing the inflammatory cytokines such as TNF-α, IL-1β, IL-6, and high mobility group box 1, via adenosine A 2A receptor signaling [14,[33][34][35]43].…”

3D‐Printed Functional Hydrogel by DNA‐Induced Biomineralization for Accelerated Diabetic Wound Healing

“…Ceravolo et al stated that DNA protects human corneal endothelial cells against H 2 O 2induced damage; Kim et al observed DNA antioxidant activity for melanocytes. [40,41] The L929 cells were exposed to 400 × 10 −6 m H 2 O 2 , which is associated with cellular dysfunction and inflammation, to establish an in vitro oxidative stress model and evaluate the antioxidant activity of DNA, which can reduce the damage caused by ROS in wound regions. When the L929 cells were cocultured with H 2 O 2 , approximately half of the cells died during the CCK-8 assay, suggesting that intracellular ROS successfully reduced L929 cell viability, as shown in Figure 6F.…”

“…[39] Moreover, DNA reduces ROS levels and exerts antioxidant activities. [40,41] Diverse in vitro, in vivo, and clinical studies suggest that tissue regeneration can be accelerated using DNA with other biomaterials. [42][43][44][45] Silica (silicon oxide [SiO 2 ]) nanoparticles (NPs), which are representative metal oxide-based nanotherapeutics, exhibit drugloading and osteogenic abilities, biocompatibility, and angiogenesis promotion.…”

“…[ 39 ] Moreover, DNA reduces ROS levels and exerts antioxidant activities. [ 40 , 41 ] Diverse in vitro, in vivo, and clinical studies suggest that tissue regeneration can be accelerated using DNA with other biomaterials. [ 42 , 43 , 44 , 45 ]…”