7, 8-Dihydroxyflavone, a TrkB receptor agonist, provides minimal protection against retinal vascular damage during oxygen-induced ischemic retinopathy

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.

Reduced BDNF expression in the auditory cortex contributed to neonatal pain-induced hearing impairment and dendritic pruning deficiency in mice

“…In the third set of experiments, male C57BL/6J mouse pups administered with intraplantar injection of 5 µL CFA (P7) randomly received i.p. injection of the selective TrkB agonist 7,8-dihydroxyflavone (DHF) (5 mg/kg/day, Selleck, USA) 15 or vehicle (3.3% DMSO) from P7 to P21. ABR was tested on P28.…”

Systemic Cytokines in Retinopathy of Prematurity

“…Brain-derived neurotrophic factor (BDNF), one of the neurotrophins, is important in both the functional and structural development of the inner retina through BDNF/TrkB signaling [ 168 , 169 ]. In mouse OIR models, the hyperoxia-exposed group had significantly lower BDNF expression than the control group reared in room air [ 170 ]. BDNF exerted a protective effect by stabilizing the retinal vasculature [ 170 ].…”

“…In mouse OIR models, the hyperoxia-exposed group had significantly lower BDNF expression than the control group reared in room air [ 170 ]. BDNF exerted a protective effect by stabilizing the retinal vasculature [ 170 ]. The lack of BDNF expression causes endothelial cell apoptosis and damages cell–cell connections [ 170 ].…”

“…BDNF exerted a protective effect by stabilizing the retinal vasculature [ 170 ]. The lack of BDNF expression causes endothelial cell apoptosis and damages cell–cell connections [ 170 ]. A consistent result was demonstrated as lower levels of serum circulating BDNF, along with neurotrophin 4, were observed in ROP infants compared to their non-ROP counterparts [ 27 , 85 , 171 , 172 ].…”