Methylene blue prevents retinal damage in an experimental model of ischemic proliferative retinopathy

MANUEL REY-FUNES, IGNACIO LARRAYOZ, JUAN FERNÁNDEZ, DANIELA CONTARTESE, FEDERICO ROLÓN, PABLO INSERRA, RICARDO MARTÍNEZ-MURILLO, JUAN LÓPEZ-COSTA, VERÓNICA DORFMAN, ALFREDO MARTÍNEZ, AND CESAR FABIÁN LOIDL

THE AMERICAN JOURNAL OF PHYSIOLOGY.

AMER PHYSIOLOGICAL SOC

Lugar: BETHESDA; Año: 2016

0002-9513

Perinatal asphyxiainduces retinal lesions, generating ischemic proliferative retinopathy,which may result in blindness. Previously, we showed that the nitrergicsystem was involved in the physiopathology of perinatal asphyxia. Herewe analyze the application of methylene blue, a well-known solubleguanylate cyclase inhibitor, as a therapeutic strategy to prevent retinopathy.Male rats (n 28 per group) were treated in different ways: 1)control group comprised born-to-term animals; 2) methylene blue groupcomprised animals born from pregnant rats treated with methylene blue(2 mg/kg) 30 and 5 min before delivery; 3) perinatal asphyxia (PA) groupcomprised rats exposed to perinatal asphyxia (20 min at 37°C); and 4)methylene blue?PA group comprised animals born from pregnant ratstreated with methylene blue (2 mg/kg) 30 and 5 min before delivery, andthen the pups were subjected to PA as above. For molecular studies,mRNA was obtained at different times after asphyxia, and tissue wascollected at 30 days for morphological and biochemical analysis. Perinatalasphyxia produced significant gliosis, angiogenesis, and thickeningof the inner retina. Methylene blue treatment reduced these parameters.Perinatal asphyxia resulted in a significant elevation of the nitrergicsystem as shown by NO synthase (NOS) activity assays, Western blotting,and (immuno)histochemistry for the neuronal isoform of NOS andNADPH-diaphorase activity. All these parameters were also normalizedby the treatment. In addition, methylene blue induced the upregulation ofthe anti-angiogenic peptide, pigment epithelium-derived factor. Applicationof methylene blue reduced morphological and biochemical parametersof retinopathy. This finding suggests the use of methylene blue as anew treatment to prevent or decrease retinal damage in the context ofischemic proliferative retinopathy