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Ignacio Larrayoz, Manuel Rey-Funes, Juan Carlos Fernández, Daniela S Contartese, Federico Rolón, Pablo Inserra, Juan J López-Costa, Verónica B Dorfman, Alfredo Martinez, Fabián Loidl; Methylene blue prevents retinal damage in a rat model of retinopathy of prematurity (ROP). Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):968.
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<br /> Perinatal asphyxia (PA) induces retinal lesions, generating ischemic proliferative retinopathy (IPR) and ROP, which may result in blindness. Previously, we have shown that the nitrergic system was involved in the physiopathology of PA-related ROP. Here we analyze the application of methylene blue (MB), a well-known guanylate cyclase inhibitor, as a therapeutic strategy to prevent IPR in a rat model of ROP.
<br /> Male rats were treated in 3 different ways: 1) CTL group comprised born to term animals; 2) PA group comprised rats exposed to perinatal asphyxia (20 min.); and 3) MB group comprised animals born from pregnant rats treated with MB (2 mg/kg) 30 and 5 min before delivery and then the pups were subjected to PA as above. mRNA was obtained 6 h after asphyxia for molecular studies and tissue was collected 30 days later for morphological and biochemical analysis. Data were statistically analyzed by ANOVA and differences were considered statistically significant when p < 0.05.
<br /> PA produced significant gliosis, angiogenesis, and thickening of the inner retina (p < 0.01). MB treatment normalized these parameters (Fig. 1). PA resulted in a significant elevation of the nitrergic system as shown by NOS activity assays, Western blotting, immunohistochemistry for nNOS, and histochemistry for NADPH-diaphorase activity (p < 0.05). All these parameters were also normalized by MB treatment. In addition, MB prevented the PA-induced upregulation of MMP9 (p < 0.05) and induced the upregulation of the antiangiogenic peptide, PEDF (p < 0.01).
<br /> Application of MB prevented morphological and biochemical parameters of IPR and ROP. This finding suggests the use of MB as a new treatment to prevent or decrease retinal damage in the context of IPR.
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