RESUMO
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-1ß, 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.
RESUMO
Fuchs endothelial corneal dystrophy (FECD) is characterized by the gradual deterioration of corneal endothelial cells (CECs) and is the most common cause of corneal transplantation worldwide. CECs apoptosis caused by oxidative stress plays a pivotal role in the pathogenesis of FECD. Antioxidant compounds have been of considerable significance as a candidate treatment in the management of corneal diseases. Based on these findings, the objective of this study was to evaluate the effects of an aloe extract with antioxidant properties, in an "in vitro" model of FECD. Human corneal epithelial (HCE) cells were preincubated with aloe extract 100 µg/mL, two hours before hydrogen peroxide (H2O2) stimulus. H2O2 challenge significantly reduced the cell viability, increased the generation of Reactive Oxygen Species (ROS) and malondialdehyde levels. Moreover, m-RNA expression and activity of Nrf-2, Catalase and Superoxide dismutase (SOD) were reduced together with an enhanced expression of IL-1ß, tumor necrosis factor-α (TNF-α), IL-6, and cyclooxygenase 2 (COX-2). Furthermore, Bcl-2, Caspase-3 and Caspase-8 expression were down-regulated while Bax was up-regulated by H2O2 stimulus. Aloe extract blunted the oxidative stress-induced inflammatory cascade triggered by H2O2 and modulated apoptosis. Aloe extract defends HCE cells from H2O2-induced injury possibly due its antioxidant and anti-inflammatory activity, indicating that eye drops containing aloe extract may be used as an adjunctive treatment for FECD.
RESUMO
BACKGROUND: The aim of this study was to compare the therapeutic effect of intravitreal treatment with ranibizumab and dexamethasone using specific swept-source optical coherence tomography retinal biomarkers in patients with diabetic macular edema (DME). METHODS: 156 treatment-naïve patients with DME were divided in two groups: 75 patients received 3 monthly intravitreal injections of ranibizumab 0.5 mg (Lucentis®) (Group 1) and 81 patients received an intravitreal implant of dexamethasone 0.7 mg (Ozurdex®) (Group 2). Patients were evaluated at baseline (V1), at three months post-treatment in Group 1, and at two months post-treatment in Group 2 (V2). Best-corrected visual acuity (BCVA) and swept source-OCT were recorded at each interval. Changes between V1 and V2 were analyzed using the Wilcoxon test and differences between the two groups of treatment were assessed using the Mann-Whitney test. Multiple regression analysis was performed to evaluate the possible OCT biomarker (CRT, ICR, CT, SND, HRS) as predictive factors for final visual acuity improvement. RESULTS: In both groups, BCVA improved (p-value < 0.0001), and a significant reduction in central retinal thickness, intra-retinal cysts, red dots, hyper-reflective spots (HRS), and serous detachment of neuro-epithelium (SDN) was observed. A superiority of dexamethasone over ranibizumab in reducing the SDN height (p-value = 0.03) and HRS (p-value = 0.01) was documented. CONCLUSIONS: Ranibizumab and dexamethasone are effective in the treatment of DME, as demonstrated by functional improvement and morphological biomarker change. DME associated with SDN and HRS represents a specific inflammatory pattern for which dexamethasone appears to be more effective.