Feng Xiaoxiao, Zhang Wenjia, Wan Tingting, Jiao Kangwei, Zhang Liwei, Li Changhui, Xiao Libo
Department of Ophthalmology, Affiliated Hospital of Yunnan University, Yunnan, China.
Yunnan Ophthalmic Disease Clinical Medical Center, Yunnan, China.
Front Mol Biosci. 2025 Aug 13;12:1636882. doi: 10.3389/fmolb.2025.1636882. eCollection 2025.
To investigate the role of the lamina cribrosa (LC) astrocytes in the autoregulatory capacity of optic nerve head (ONH) vessels and to explore the underlying molecular mechanisms.
The Oxygen-glucose deprivation/reperfusion model (OGD/R) was constructed to examine the changes in cell morphology and protein expression in LC astrocytes. LC astrocytes were co-cultured with vascular smooth muscle cells (VSMCs) to detect the role of LC astrocytes in the autoregulatory function of vessels.
The partial pressure of oxygen (PO) in the supernatant of LC astrocytes was significantly lower following OGD, and this reduction was more pronounced with longer OGD durations. OGD inhibited proliferation and promoted apoptosis in LC astrocytes, with longer OGD durations correlating with decreased proliferation and increased apoptosis. Reoxygenation following 1 h of OGD led to upregulation of GFAP, mTOR, cPLA protein expression and supernatant PGE2 concentration in LC astrocytes, an effect that can be attenuated by the mTOR inhibitor. Co-culturing with LC astrocyte resulted in increased expression of MYPT1 protein in VSMCs, and the VSMCs exhibited a relaxed morphology.
Under OGD/R conditions, LC astrocyte were activated through the mTOR pathway, leading to increased secretion of PGE, which locally regulates the dilation of VSMCs. In conclusion, LC astrocytes may regulate local blood flow in the ONH.
研究筛板(LC)星形胶质细胞在视神经乳头(ONH)血管自动调节能力中的作用,并探讨其潜在的分子机制。
构建氧糖剥夺/再灌注模型(OGD/R),以检测LC星形胶质细胞的细胞形态和蛋白质表达变化。将LC星形胶质细胞与血管平滑肌细胞(VSMC)共培养,以检测LC星形胶质细胞在血管自动调节功能中的作用。
OGD后,LC星形胶质细胞上清液中的氧分压(PO)显著降低,且随着OGD时间延长,这种降低更为明显。OGD抑制LC星形胶质细胞的增殖并促进其凋亡,OGD时间越长,增殖减少和凋亡增加越明显。OGD 1小时后的复氧导致LC星形胶质细胞中GFAP、mTOR、cPLA蛋白表达上调和上清液PGE2浓度升高,mTOR抑制剂可减弱这种作用。与LC星形胶质细胞共培养导致VSMC中MYPT1蛋白表达增加,且VSMC呈现松弛形态。
在OGD/R条件下,LC星形胶质细胞通过mTOR途径被激活,导致PGE分泌增加,从而局部调节VSMC的舒张。总之,LC星形胶质细胞可能调节ONH的局部血流。