Roth Steven, Dreixler John C, Mathew Biji, Balyasnikova Irina, Mann Jacob R, Boddapati Venkat, Xue Lai, Lesniak Maciej S
Department of Anesthesiology, University of Illinois, Illinois, United States 3Department of Anesthesia and Critical Care, University of Chicago, Illinois, United States.
Department of Anesthesia and Critical Care, University of Chicago, Illinois, United States.
Invest Ophthalmol Vis Sci. 2016 Jun 1;57(7):3522-32. doi: 10.1167/iovs.15-17381.
We have previously demonstrated the protective effect of bone marrow stem cell (BMSC)-conditioned medium in retinal ischemic injury. We hypothesized here that hypoxic preconditioning of stem cells significantly enhances the neuroprotective effect of the conditioned medium and thereby augments the protective effect in ischemic retina.
Rats were subjected to retinal ischemia by increasing intraocular pressure to 130 to 135 mm Hg for 55 minutes. Hypoxic-preconditioned, hypoxic unconditioned, or normoxic medium was injected into the vitreous 24 hours after ischemia ended. Recovery was assessed 7 days after injections by comparing electroretinography measurements, histologic examination, and apoptosis (TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay). To compare proteins secreted into the medium in the groups and the effect of hypoxic exposure, we used rat cytokine arrays.
Eyes injected with hypoxic BMSC-conditioned medium 24 hours after ischemia demonstrated significantly enhanced return of retinal function, decreased retinal ganglion cell layer loss, and attenuated apoptosis compared to those administered normoxic or hypoxic unconditioned medium. Hypoxic-preconditioned medium had 21 significantly increased protein levels compared to normoxic medium.
The medium from hypoxic-preconditioned BMSCs robustly restored retinal function and prevented cell loss after ischemia when injected 24 hours after ischemia. The protective effect was even more pronounced than in our previous studies of normoxic conditioned medium. Prosurvival signals triggered by the secretome may play a role in this neuroprotective effect.
我们之前已证明骨髓干细胞（BMSC）条件培养基对视网膜缺血性损伤具有保护作用。我们在此推测，干细胞的低氧预处理可显著增强条件培养基的神经保护作用，从而增强对缺血视网膜的保护作用。
通过将眼压升高至130至135毫米汞柱持续55分钟，使大鼠遭受视网膜缺血。在缺血结束24小时后，将低氧预处理的、低氧未预处理的或常氧培养基注入玻璃体。注射7天后，通过比较视网膜电图测量、组织学检查和凋亡（TUNEL，末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法）来评估恢复情况。为了比较各组培养基中分泌的蛋白质以及低氧暴露的影响，我们使用了大鼠细胞因子阵列。
与注射常氧或低氧未预处理培养基的大鼠相比，在缺血24小时后注射低氧BMSC条件培养基的大鼠，视网膜功能恢复显著增强，视网膜神经节细胞层损失减少，凋亡减轻。与常氧培养基相比，低氧预处理培养基中有21种蛋白质水平显著升高。
在缺血24小时后注射时，低氧预处理BMSC的培养基能有力地恢复视网膜功能并防止缺血后细胞丢失。这种保护作用比我们之前对常氧条件培养基的研究更为明显。分泌组触发的促生存信号可能在这种神经保护作用中发挥作用。
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