Department of Physiology, Third Faculty of Medicine, Charles University, Ke Karlovu 4, 120 00 Prague, Czech Republic.
Department of Health Care and Population Protection, Faculty of Biomedical Engineering, Czech Technical University in Prague, Sitna Sq. 3105, 272 01 Kladno, Czech Republic.
Int J Mol Sci. 2022 Aug 3;23(15):8615. doi: 10.3390/ijms23158615.
High-contrast visual stimulation promotes retinal regeneration and visual function, but the underlying mechanism is not fully understood. Here, we hypothesized that Müller cells (MCs), which express neurotrophins such as brain-derived neurotrophic factor (BDNF), could be key players in this retinal plasticity process. This hypothesis was tested by conducting in vivo and in vitro high-contrast stimulation of adult mice and MCs. Following stimulation, we examined the expression of BDNF and its inducible factor, VGF, in the retina and MCs. We also investigated the alterations in the expression of VGF, nuclear factor kappa B (NF-κB) and pro-inflammatory mediators in MCs, as well as their capacity to proliferate and develop a neurogenic or reactive gliosis phenotype after high-contrast stimulation and treatment with BDNF. Our results showed that high-contrast stimulation upregulated BDNF levels in MCs in vivo and in vitro. The additional BDNF treatment significantly augmented VGF production in MCs and their neuroprotective features, as evidenced by increased MC proliferation, neurodifferentiation, and decreased expression of the pro-inflammatory factors and the reactive gliosis marker GFAP. These results demonstrate that high-contrast stimulation activates the neurotrophic and neuroprotective properties of MCs, suggesting their possible direct involvement in retinal neuronal survival and improved functional outcomes in response to visual stimulation.
高对比度视觉刺激可促进视网膜再生和视觉功能，但其中的潜在机制尚未完全阐明。在此，我们假设 Müller 细胞（MCs）可能是这种视网膜可塑性过程中的关键角色，因为它们表达神经营养因子如脑源性神经营养因子（BDNF）。通过对成年小鼠和 MCs 进行体内和体外的高对比度刺激实验，对这一假说进行了检验。刺激后，我们检测了视网膜和 MCs 中 BDNF 及其诱导因子 VGF 的表达情况。我们还研究了 VGF、核因子 kappa B（NF-κB）和促炎介质在 MCs 中的表达变化，以及它们在高对比度刺激和 BDNF 处理后增殖和发展为神经发生或反应性胶质增生表型的能力。研究结果表明，高对比度刺激可上调体内和体外 MCs 中的 BDNF 水平。额外的 BDNF 处理可显著增加 MCs 中 VGF 的产生及其神经保护特性，这表现为 MC 增殖、神经分化增加，以及促炎因子和反应性胶质增生标志物 GFAP 的表达减少。这些结果表明，高对比度刺激可激活 MCs 的神经营养和神经保护特性，这提示它们可能直接参与了视网膜神经元的存活，并改善了对视觉刺激的功能恢复。
