Melatonin protects inner retinal neurons of newborn mice after hypoxia‐ischemia

Abstract

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 antiapoptotic and neuroprotective effects in inner retinal neurons after hypoxia-ischemia, at least partly due to modulation of the BDNF-TrkB pathway.

lncRNA BDNF-AS Attenuates Propofol-Induced Apoptosis in HT22 Cells by Modulating the BDNF/TrkB Pathway

“…Matusica et al [ 21 ] indicated that BDNF enables P75 (NTR)-derived trophic cell permeapeptides (c29) to promote neuronal survival through the TrkB-dependent signaling pathway in vitro and in vivo. The BDNF/TrkB pathway in learning and memory [ 22 ], chronic pain [ 23 ], and retinopathy [ 24 ] has been deeply studied, but there are few studies on neuronal apoptosis. BDNF-AS is a natural antisense transcript that inhibits the transcription of BDNF [ 15 , 25 ].…”

Occurrence of Oxidative Stress and Premature Senescence in the Anterior Segment of Acute Primary Angle-Closure Eyes

“…Immunofluorescence of iridal frozen sections and flat mounts of anterior lens capsule was performed as described previously. 27 – 29 Briefly, the tissues were permeated for 20 minutes and blocked with 5% normal goat serum for two hours at 25°C. Then, the tissues were incubated with primary antibodies overnight at 4°C, followed by a corresponding secondary antibody for two hours ( Supplementary Table S3 ).…”

A Novel Hypoxia-inducible Factor 1α Inhibitor KC7F2 Attenuates Oxygen-induced Retinal Neovascularization

“…Immunofluorescent staining of whole retinal mounts, frozen sections, and HUVEC was performed as described previously. 28 , 29 All fluorescence images were taken using confocal laser scanning microscopy (LSM880, Carl Zeiss, Jena, Germany). For whole retinal mounts, six retinas were analyzed per experimental group and the extent of neovascular or avascular area were expressed as the percentage of the number of pixels in the neovascular tuft area/ avascular area relative to the number of pixels in the total retinal area.…”

“…HE staining was applied as described previously. 28 Sections were imaged using a light microscope (Leica, Frankfurt, Germany) to measure the number of vitreoretinal neovascular cells nuclei. A quantitative approach to HE staining kept consistent with what was detailed elsewhere in this article for the quantitation of the frozen sections.…”