Methylene blue postnatal application protects from retinal damage induced by perinatal asphyxia

Abstract

Purpose : Perinatal asphyxia (PA) induces retinal lesions, generating ischemic proliferative retinopathy (IPR) and retinopathy of prematurity (ROP), which may result in blindness. Methylene blue (MB), a well-known nitric oxide synthase (NOS) inhibitor, has been recently proposed as a protective agent against retinal damage. In the present work we analyze the protective role of MB therapeutic administration against retinal damage induced by PA

Methods : Rat pups were treated in 4 different ways: 1) CTL group comprised born to term animals; 2) MB group comprised born to term animals treated with MB (2 mg/kg, s.c.); 3) PA group comprised rat pups exposed to perinatal asphyxia for 20 min (water bath immersion); and 4) MB-PA group comprised animals subjected to PA and treated with MB (2 mg/kg, s.c.) 60 min after asphixia. For molecular studies, mRNA was obtained 2 to 24h after asphyxia. For morphological and biochemical analysis tissue was collected 5 and 30 days later. Data were statistically analyzed by ANOVA and differences were considered statistically significant when p < 0.05

Results : In newborn retinas, MB administration suppressed PA-induced upregulation of iNOS, VEFG and MMP9 mRNA. Five days after birth, PA group presented extensive ganglion cell death, as shown by TUNEL assay. MB treatment reduced TUNEL-positive cells by 50% (p < 0.001). At 30 days, animals subjected to PA showed a significant increase of inner retina thickness which was prevented by MB treatment (p < 0.05)

Conclusions : Application of MB, 1 hour after PA, reduced the morphological and biochemical parameters of IPR and ROP in a PA model. This finding suggests MB could be applied as an ophthalmological therapy following acute cases of obstetric complications to prevent or decrease retinal damage in the context of IPR and ROP

* RP, *JCF and *MR-F contributed equally
# CFL and # IML contributed equally

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.