Riemann Sarah, Kolibabka Matthias, Busch Stephanie, Lin Jihong, Hoffmann Sigrid, Gretz Norbert, Feng Yuxi, Wohlfart Paulus, Hammes Hans-Peter
5th Medical Department, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Front Physiol. 2021 Apr 26;12:660164. doi: 10.3389/fphys.2021.660164. eCollection 2021.
Vascular dysfunction and vasoregression are hallmarks of a variety of inflammatory central nervous system disorders and inflammation-related retinal diseases like diabetic retinopathy. Activation of microglia and the humoral innate immune system are contributing factors. Anti-inflammatory approaches have been proposed as therapies for neurovascular diseases, which include the modulation of microglial activation. The present study aimed at investigating the effects of microglial activation by clodronate-coated liposomes on vasoregression in a model of retinal degeneration. Clodronate treatment over 5 weeks led to an increase in activated CD74 microglia and completely prevented acellular capillaries and pericyte loss. Gene expression analyses indicated that vasoprotection was due to the induction of vasoprotective factors such as , , and while expression of pro-inflammatory genes remained unchanged. We concluded that activated microglia led to a shift toward induction of pleiotropic protective pathways supporting vasoprotection in neurovascular retinal diseases.
血管功能障碍和血管消退是多种炎症性中枢神经系统疾病以及炎症相关视网膜疾病(如糖尿病性视网膜病变)的标志。小胶质细胞和体液固有免疫系统的激活是促成因素。抗炎方法已被提议作为神经血管疾病的治疗手段,其中包括调节小胶质细胞的激活。本研究旨在调查氯膦酸盐包被脂质体激活小胶质细胞对视网膜变性模型中血管消退的影响。超过5周的氯膦酸盐治疗导致活化的CD74小胶质细胞增加,并完全防止了无细胞毛细血管和周细胞丢失。基因表达分析表明,血管保护是由于诱导了血管保护因子,如 、 和 ,而促炎基因的表达保持不变。我们得出结论,活化的小胶质细胞导致向诱导多效性保护途径的转变,从而支持神经血管性视网膜疾病中的血管保护。