Methylene Blue Prevents Retinal Damage Caused by Perinatal Asphyxia in the Rat.

angiogenesis apoptosis electroretinography inner retinal thickness methylene blue perinatal asphyxia

Journal

Frontiers in cellular neuroscience
ISSN: 1662-5102
Titre abrégé: Front Cell Neurosci
Pays: Switzerland
ID NLM: 101477935

Informations de publication

Date de publication:
2020
Historique:
received: 14 01 2020
accepted: 12 05 2020
entrez: 26 6 2020
pubmed: 26 6 2020
medline: 26 6 2020
Statut: epublish

Résumé

Perinatal asphyxia (PA) is responsible for a large proportion of neonatal deaths and numerous neurological sequelae, including visual dysfunction and blindness. In PA, the retina is exposed to ischemia/reoxygenation, which results in nitric oxide (NO) overproduction and neurotoxicity. We hypothesized that methylene blue (MB), a guanylyl cyclase inhibitor, and free-radical scavenger currently used in the clinic, may block this pathway and prevent PA-induced retinal degeneration. Male rat pups were subjected to an experimental model of PA. Four groups were studied: normally delivered (CTL), normally delivered treated with 2 mg Kg-1 MB (MB), exposed to PA for 20 min at 37°C (PA), and exposed to PA and, then, treated with MB (PA-MB). Scotopic electroretinography performed 45 days after birth showed that PA animals had significant defects in the a- and b-waves and oscillatory potentials (OP). The same animals presented a significant increase in the thickness of the inner retina and a large number of TUNEL-positive cells. All these physiological and morphological parameters were significantly prevented by the treatment with MB. Gene expression analysis demonstrated significant increases in iNOS, MMP9, and VEGF in the eyes of PA animals, which were prevented by MB treatment. In conclusion, MB regulates key players of inflammation, matrix remodeling, gliosis, and angiogenesis in the eye and could be used as a treatment to prevent the deleterious visual consequences of PA. Given its safety profile and low cost, MB may be used clinically in places where alternative treatments may be unavailable.

Identifiants

pubmed: 32581722
doi: 10.3389/fncel.2020.00157
pmc: PMC7289067
doi:

Types de publication

Journal Article

Langues

eng

Pagination

157

Informations de copyright

Copyright © 2020 Fernández, Peláez, Rey-Funes, Soliño, Contartese, Dorfman, López-Costa, Larrayoz, Loidl and Martínez.

Références

Invest Ophthalmol Vis Sci. 2005 Aug;46(8):2736-47
pubmed: 16043845
Prog Retin Eye Res. 2007 May;26(3):205-38
pubmed: 17337232
J Neurosci Res. 2011 May;89(5):729-43
pubmed: 21337363
Sci Rep. 2017 Jul 31;7(1):6966
pubmed: 28761115
Ann R Coll Surg Engl. 2014 Oct;96(7):526-9
pubmed: 25245732
Prog Retin Eye Res. 2004 Jan;23(1):91-147
pubmed: 14766318
Invest Ophthalmol Vis Sci. 2013 Apr 23;54(4):2836-46
pubmed: 23471892
Ann Emerg Med. 1999 Nov;34(5):646-56
pubmed: 10533013
Front Cell Neurosci. 2020 Mar 24;14:52
pubmed: 32265657
J Clin Invest. 2007 Mar;117(3):576-86
pubmed: 17332885
Adv Drug Deliv Rev. 2018 Feb 15;126:145-161
pubmed: 29625138
Clin Sci (Lond). 2017 Jul 5;131(15):1763-1780
pubmed: 28679845
J Cardiothorac Vasc Anesth. 2014 Apr;28(2):e12-3
pubmed: 24630472
Anesth Analg. 2015 Jun;120(6):1331-6
pubmed: 25794112
Neurosci Lett. 2014 Apr 17;565:30-8
pubmed: 24406153
Med Arch. 2014;68(2):102-5
pubmed: 24937932
Pediatr Neurol. 1991 Sep-Oct;7(5):317-25
pubmed: 1764132
Am J Physiol Regul Integr Comp Physiol. 2016 Jun 1;310(11):R1011-9
pubmed: 26984891
Fa Yi Xue Za Zhi. 2013 Feb;29(1):5-11, 16
pubmed: 23646494
Invest Ophthalmol Vis Sci. 2015 Aug;56(9):5182-93
pubmed: 26244294
J Comp Neurol. 2007 May 1;502(1):734-45
pubmed: 17436468
Lancet. 2015 Jan 31;385(9966):430-40
pubmed: 25280870
Invest Ophthalmol Vis Sci. 2014 Sep 04;55(10):6350-7
pubmed: 25190658
Invest Ophthalmol Vis Sci. 2018 Aug 1;59(10):3879-3888
pubmed: 30073348
J Surg Res. 2007 Dec;143(2):311-9
pubmed: 17826794
Transl Stroke Res. 2020 Mar 24;:
pubmed: 32207038
BMJ Open Qual. 2018 Sep 4;7(3):e000231
pubmed: 30234170
Physiol Behav. 2000 Jan;68(3):263-9
pubmed: 10716534
Eur Rev Med Pharmacol Sci. 2017 Dec;21(23):5361-5369
pubmed: 29243776
PLoS One. 2018 Sep 20;13(9):e0204364
pubmed: 30235340
Free Radic Biol Med. 2005 Jul 1;39(1):26-50
pubmed: 15925277
Early Hum Dev. 2018 Oct;125:1-7
pubmed: 30144709
FASEB J. 2008 Mar;22(3):703-12
pubmed: 17928358
Neurotox Res. 2006 Jan;9(1):47-57
pubmed: 16464752
J Enzyme Inhib Med Chem. 2016;31(sup1):177-183
pubmed: 27028474
Neurotox Res. 2009 Apr;15(3):260-73
pubmed: 19384599
J Thorac Cardiovasc Surg. 2004 Feb;127(2):608
pubmed: 14762391
Br J Pharmacol. 1998 Nov;125(6):1158-63
pubmed: 9863642
Eur J Pharmacol. 2018 Aug 15;833:290-297
pubmed: 29890158
Pediatrics. 2013 Oct;132(4):e952-9
pubmed: 24019409
Cochrane Database Syst Rev. 2018 Oct 16;10:CD007419
pubmed: 30325017
Arch Dis Child Fetal Neonatal Ed. 2019 May;104(3):F285-F292
pubmed: 29997167
Adv Exp Med Biol. 2014;801:275-81
pubmed: 24664708
Lab Invest. 2015 Aug;95(8):914-24
pubmed: 26097999
N Engl J Med. 2004 Nov 4;351(19):1985-95
pubmed: 15525724

Auteurs

Juan Carlos Fernández (JC)

Instituto de Biología Celular y Neurociencia "Prof. E. de Robertis", Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Primera Cátedra de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

Rafael Peláez (R)

Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain.

Manuel Rey-Funes (M)

Instituto de Biología Celular y Neurociencia "Prof. E. de Robertis", Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

Manuel Soliño (M)

Instituto de Biología Celular y Neurociencia "Prof. E. de Robertis", Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

Daniela S Contartese (DS)

Instituto de Biología Celular y Neurociencia "Prof. E. de Robertis", Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

Verónica B Dorfman (VB)

Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y Diagnóstico (CEBBAD), Universidad Maimónides, Buenos Aires, Argentina.

Juan José López-Costa (JJ)

Instituto de Biología Celular y Neurociencia "Prof. E. de Robertis", Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

Ignacio M Larrayoz (IM)

Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain.

César F Loidl (CF)

Instituto de Biología Celular y Neurociencia "Prof. E. de Robertis", Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

Alfredo Martínez (A)

Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain.

Classifications MeSH