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

Publications // Sheibani Lab // Jan 01 2021

PubMed ID: 34855884

Author(s): Zaitoun IS, Song YS, Suscha A, El Ragaby M, Sorenson CM, Sheibani N. 7, 8-Dihydroxyflavone, a TrkB receptor agonist, provides minimal protection against retinal vascular damage during oxygen-induced ischemic retinopathy. PLoS One. 2021 Dec 2;16(12):e0260793. doi: 10.1371/journal.pone.0260793. eCollection 2021. PMID 34855884

Journal: Plo S One, Volume 16, Issue 12, 2021

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.