Concentrated conditioned media from adipose tissue–derived mesenchymal stem cells (ASC-CCM) show promise for retinal degenerative diseases. In this study, we hypothesized that ASC-CCM could rescue retinal damage and thereby improve visual function by acting through Müller glia in mild traumatic brain injury (mTBI). Adult C57Bl/6 mice were subjected to a 50-psi air pulse on the left side of the head, resulting in an mTBI. After blast injury, 1 μL (∼100 ng total protein) of human ASC-CCM was delivered intravitreally and followed up after 4 weeks for visual function assessed by electroretinogram and histopathological markers for Müller cell-related markers. Blast mice that received ASC-CCM, compared with blast mice that received saline, demonstrated a significant improvement in a- and b-wave response correlated with a 1.3-fold decrease in extracellular glutamate levels and a concomitant increase in glutamine synthetase (GS), as well as the glutamate transporter (GLAST) in Müller cells. Additionally, an increase in aquaporin-4 (AQP4) in Müller cells in blast mice received saline restored to normal levels in blast mice that received ASC-CCM. In vitro studies on rMC-1 Müller glia exposed to 100 ng/mL glutamate or RNA interference knockdown of GLAST expression mimicked the increased Müller cell glial fibrillary acidic protein (a marker of gliosis) seen with mTBI, and suggested that an increase in glutamate and/or a decrease in GLAST might contribute to the Müller cell activation in vivo. Taken together, our data suggest a novel neuroprotective role for ASC-CCM in the rescue of the visual deficits and pathologies of mTBI via restoration of Müller cell health.

中文翻译：

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脂肪组织来源的间充质干细胞浓缩条件培养基改变轻度创伤性脑损伤后视网膜中谷氨酸调节蛋白和水通道蛋白 4 的表达模式

来自脂肪组织来源的间充质干细胞 (ASC-CCM) 的浓缩条件培养基显示出治疗视网膜退行性疾病的前景。在这项研究中，我们假设 ASC-CCM 可以通过 Müller 胶质细胞在轻度创伤性脑损伤 (mTBI) 中发挥作用来挽救视网膜损伤，从而改善视觉功能。成年 C57Bl/6 小鼠在头部左侧接受 50 psi 空气脉冲，导致 mTBI。爆炸伤后，玻璃体内输送 1 μL（~100 ng 总蛋白）人 ASC-CCM，4 周后通过视网膜电图和 Müller 细胞相关标志物的组织病理学标志物评估视觉功能。接受 ASC-CCM 的 Blast 小鼠与接受盐水的 Blast 小鼠相比，显示出与 1 相关的 a 波和 b 波反应的显着改善。Müller 细胞中的细胞外谷氨酸水平降低 3 倍，谷氨酰胺合成酶 (GS) 和谷氨酸转运蛋白 (GLAST) 随之增加。此外，在接受 ASC-CCM 的爆炸小鼠中，接受盐水的爆炸小鼠的 Müller 细胞中水通道蛋白 4 (AQP4) 的增加恢复到正常水平。rMC-1 Müller 胶质细胞暴露于 100 ng/mL 谷氨酸或 GLAST 表达的 RNA 干扰敲低的体外研究模拟了 mTBI 观察到的 Müller 细胞胶质纤维酸性蛋白（胶质增生的标志物）增加，并表明谷氨酸和/ 或 GLAST 的降低可能有助于体内 Müller 细胞的活化。总之，我们的数据表明 ASC-CCM 在通过恢复 Müller 细胞健康来挽救 mTBI 的视觉缺陷和病理方面具有新的神经保护作用。