Abstract
Retinopathy of prematurity (ROP) is one of the main causes of blindness in children worldwide. Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), play critical protective roles in the development and function of neurons and vasculature. Lack of BDNF expression results in increased endothelial cell apoptosis and reduced endothelial cell-cell contact. Premature babies who develop ROP tend to have lower serum BDNF levels. BDNF expression is also significantly lower in mouse retinas following exposure to hyperoxia compared to those reared in room air. Specifically, BDNF promotes angiogenic tube formation of endothelial cells (EC), and it is considered an EC survival factor required for stabilization of intramyocardial vessels. We hypothesized that the activation of TrkB receptor protects retinal vasculature in the mice during oxygen-induced ischemic retinopathy (OIR), a model of ROP. To test this hypothesis, we treated neonatal mice with 7,8-dihydroxyflavone (DHF) (5 mg/kg body weight), a TrkB receptor agonist. We examined its potential protective effects on retinal vessel obliteration and neovascularization, two hallmarks of ROP and OIR. We found that retinas from DHF treated postnatal day 8 (P8) and P12 mice have similar levels of vessel obliteration as retinas from age-matched control mice subjected to OIR. Similarly, DHF showed no significant effect on mitigation of retinal neovascularization during OIR in P17 mice. Collectively, our studies demonstrate that the TrkB receptor agonist DHF provides no significant protective effects during OIR.
Highlights
Retinopathy of prematurity (ROP) is a major cause of visual impairment and blindness that affects a significant proportion of children born prematurely in the USA [1]
Along with its roles in normal vascular development, studies have reported some evidence that Brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling is involved in the regulation of vascular diseases, such as ROP
Retinal vascular development and homeostasis are strictly controlled by oxygen and nutrients needs of the neural retina
Summary
Retinopathy of prematurity (ROP) is a major cause of visual impairment and blindness that affects a significant proportion of children born prematurely in the USA [1]. Current medical interventions for ROP are achieved by laser ablation of the avascular part of the retina [3] and by intravitreal injection of an antibody to neutralize excess vascular endothelial growth factor (VEGF) [4,5,6,7]. Along with its roles in normal vascular development, studies have reported some evidence that BDNF/TrkB signaling is involved in the regulation of vascular diseases, such as ROP. To the best of our knowledge, this is the first report that examines the in vivo effect of DHF on retinal vasculature integrity during OIR
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