June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Methylene blue prevents retinal damage in a rat model of retinopathy of prematurity (ROP)
Author Affiliations & Notes
  • Ignacio Larrayoz
    Angiogenesis, Centro de Investigacion Biomedica de La Rioja (CIBIR), Logroño, Spain
  • Manuel Rey-Funes
    Laboratorio de Neuropatologia Experimental, Instituto de Biologia Celular y Neurociencia "Prof. E. De Robertis", Buenos Aires, Argentina
  • Juan Carlos Fernández
    Primera Cátedra de Farmacología, Universidad de Buenos Aires, Buenos Aires, Argentina
  • Daniela S Contartese
    Laboratorio de Neuropatologia Experimental, Instituto de Biologia Celular y Neurociencia "Prof. E. De Robertis", Buenos Aires, Argentina
  • Federico Rolón
    Laboratorio de Neuropatologia Experimental, Instituto de Biologia Celular y Neurociencia "Prof. E. De Robertis", Buenos Aires, Argentina
  • Pablo Inserra
    Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y Diagnóstico (CEBBAD), Universidad Maimónides, Buenos Aires, Argentina
  • Juan J López-Costa
    Laboratorio de Neuropatologia Experimental, Instituto de Biologia Celular y Neurociencia "Prof. E. De Robertis", Buenos Aires, Argentina
  • Verónica B Dorfman
    Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y Diagnóstico (CEBBAD), Universidad Maimónides, Buenos Aires, Argentina
  • Alfredo Martinez
    Angiogenesis, Centro de Investigacion Biomedica de La Rioja (CIBIR), Logroño, Spain
  • Fabián Loidl
    Laboratorio de Neuropatologia Experimental, Instituto de Biologia Celular y Neurociencia "Prof. E. De Robertis", Buenos Aires, Argentina
    Facultad de Medicina, Universidad Católica de Cuyo, San Juan, Argentina
  • Footnotes
    Commercial Relationships Ignacio Larrayoz, None; Manuel Rey-Funes, None; Juan Fernández, None; Daniela Contartese, None; Federico Rolón, None; Pablo Inserra, None; Juan López-Costa, None; Verónica Dorfman, None; Alfredo Martinez, None; Fabián Loidl, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 968. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

<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.

 
Methods
 

<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.

 
Results
 

<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).

 
Conclusions
 

<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.  

 
<br /> Figure 1. Representative micrographs of the inner retina in rats of the experimental groups CTL (A,D), PA (B,E), and MB (C,F) immunostained with an antibody against GFAP (green, A-C) or with tomato lectin (D-F). Using these sections, the thickness of the inner retina (G) and the number of blood vessels per microscopic field (H) were quantified. INL: Inner nuclear layer; IPL: Inner plexiform layer; IR: Inner retina. Bars represent the mean ± SD of all measurements (n=4 animals, 6 sections per animal). The asterisks represent statistically significant differences with the CTL group. *: p<0.05; **: p<0.01.
 
<br /> Figure 1. Representative micrographs of the inner retina in rats of the experimental groups CTL (A,D), PA (B,E), and MB (C,F) immunostained with an antibody against GFAP (green, A-C) or with tomato lectin (D-F). Using these sections, the thickness of the inner retina (G) and the number of blood vessels per microscopic field (H) were quantified. INL: Inner nuclear layer; IPL: Inner plexiform layer; IR: Inner retina. Bars represent the mean ± SD of all measurements (n=4 animals, 6 sections per animal). The asterisks represent statistically significant differences with the CTL group. *: p<0.05; **: p<0.01.

 
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