János Szentágothai Research Centre, University of Pécs, 7624 Pécs, Hungary.
Retinal Electrical Synapses Research Group, National Brain Research Program (NAP 2.0), Hungarian Academy of Sciences, 1051 Budapest, Hungary.
Int J Mol Sci. 2020 Apr 5;21(7):2522. doi: 10.3390/ijms21072522.
The nervous system demands an adequate oxygen and metabolite exchange, making pericytes (PCs), the only vasoactive cells on the capillaries, essential to neural function. Loss of PCs is a hallmark of multiple diseases, including diabetes, Alzheimer's, amyotrophic lateral sclerosis (ALS) and Parkinson's. Platelet-derived growth factor receptors (PDGFRs) have been shown to be critical to PC function and survival. However, how PDGFR-mediated PC activity affects vascular homeostasis is not fully understood. Here, we tested the hypothesis that imatinib, a chemotherapeutic agent and a potent PDGFR inhibitor, alters PC distribution and thus induces vascular atrophy. We performed a morphometric analysis of the vascular elements in sham control and imatinib-treated NG2-DsRed mice. Vascular morphology and the integrity of the blood-retina barrier (BRB) were evaluated using blood albumin labeling. We found that imatinib decreased the number of PCs and blood vessel (BV) coverage in all retinal vascular layers; this was accompanied by a shrinkage of BV diameters. Surprisingly, the total length of capillaries was not altered, suggesting a preferential effect of imatinib on PCs. Furthermore, blood-retina barrier disruption was not evident. In conclusion, our data suggest that imatinib could help in treating neurovascular diseases and serve as a model for PC loss, without BRB disruption.
神经系统需要充足的氧气和代谢物交换，因此周细胞（PCs）作为毛细血管上唯一具有血管活性的细胞，对于神经功能至关重要。PCs 的丧失是多种疾病的标志，包括糖尿病、阿尔茨海默病、肌萎缩侧索硬化症（ALS）和帕金森病。血小板衍生生长因子受体（PDGFRs）被证明对 PC 功能和存活至关重要。然而，PDGFR 介导的 PC 活性如何影响血管稳态尚不完全清楚。在这里，我们检验了这样一个假设，即伊马替尼，一种化疗药物和一种有效的 PDGFR 抑制剂，改变 PC 的分布，从而诱导血管萎缩。我们对 sham 对照和伊马替尼处理的 NG2-DsRed 小鼠中的血管成分进行了形态计量学分析。使用血液白蛋白标记评估血管形态和血视网膜屏障（BRB）的完整性。我们发现伊马替尼减少了所有视网膜血管层中的 PC 和血管（BV）覆盖率；这伴随着 BV 直径的缩小。令人惊讶的是，毛细血管的总长度没有改变，这表明伊马替尼对 PC 具有优先作用。此外，血视网膜屏障的破坏并不明显。总之，我们的数据表明，伊马替尼可能有助于治疗神经血管疾病，并可作为 PC 丧失的模型，而不会破坏 BRB。
