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Melatonin protects inner retinal neurons of newborn mice after hypoxia‐ischemia
Author(s) -
Huang Rong,
Xu Yue,
Lu Xi,
Tang Xiaoyu,
Lin Jianqiang,
Cui Kaixuan,
Yu Shanshan,
Shi Yuxun,
Ye Dan,
Liu Yizhi,
Liang Xiaoling
Publication year - 2021
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12716
Subject(s) - melatonin , neuroprotection , tropomyosin receptor kinase b , retinal , melatonin receptor , retina , ischemia , endocrinology , biology , medicine , hypoxia (environmental) , neurotrophic factors , neuroscience , receptor , chemistry , biochemistry , organic chemistry , oxygen
Retinopathy of prematurity is a vision‐threatening disease associated with retinal hypoxia‐ischemia, leading to the death of retinal neurons and chronic neuronal degeneration. During this study, we used the oxygen‐induced retinopathy mice model to mimic retinal hypoxia‐ischemia phenotypes to investigate further the neuroprotective effect of melatonin on neonatal retinal neurons. Melatonin helped maintain relatively normal inner retinal architecture and thickness and preserve inner retinal neuron populations in avascular areas by rescuing retinal ganglion and bipolar cells, and horizontal and amacrine neurons, from apoptosis. Meanwhile, melatonin recovered visual dysfunction, as reflected by the improved amplitudes and implicit times of a‐wave, b‐wave, and oscillatory potentials. Additionally, elevated cleaved caspase‐3 and Bax protein levels and reduced Bcl‐2 protein levels in response to hypoxia‐ischemia were diminished after melatonin treatment. Moreover, melatonin increased BDNF and downstream phospho‐TrkB/Akt/ERK/CREB levels. ANA‐12, a TrkB receptor antagonist, antagonized these melatonin actions and reduced melatonin‐induced neuroprotection. Furthermore, melatonin rescued the reduction in melatonin receptor expression. This study suggests that melatonin exerted anti‐apoptotic and neuroprotective effects in inner retinal neurons after hypoxia‐ischemia, at least partly due to modulation of the BDNF‐TrkB pathway.