Nerves and Neovessels Inhibit Each Other in the Cornea
Nerves and Neovessels Inhibit Each Other in the Cornea
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DOI：
10.1167/iovs.11-8379
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发表时间：
2013-01-01
影响因子：
4.4
通讯作者：
Dana, Reza
中科院分区：
文献类型：
--
作者：
Ferrari, Giulio;Hajrasouliha, Amir R.;Dana, Reza
目的。为了评估角膜中血管和神经网络的调节串扰，将b-成纤维细胞生长因子微球(80 Ng)植入健康C57BL/6小鼠的角膜颞侧。术后7d取材，免疫荧光染色观察新生血管和神经的变化。下一组小鼠接受了三叉神经立体定向电解(TSE)或假手术，以消融三叉神经的眼支。术后用PECAM-1(CD31)免疫组织化学方法检测血管生长情况。在TSE或假手术后的另一组小鼠中，取角膜进行ELISA(VEGFR3和色素上皮衍生因子[PEDF])和定量RT-PCR(VEGFR3、PEDF和CD45)。用免疫组织化学方法检测PEDF、VEGFR3、β-3微管蛋白、CD45、CD11b和F4/80在角膜新生血管中的表达。结果：在角膜新生血管形成区未检测到神经，而在无新生血管的区域有神经存在。相反，在去神经支配后7天，在角膜中检测到显著的血管生成，这与VEGFR3表达显著减少(57.5%，P=0.001)和PEDF蛋白表达显著减少(减少%，P<；0.001)有关。免疫组织化学染色显示VEGFR3在角膜上皮层的表达减少。最后，观察到炎症细胞的渗入，包括巨噬细胞。结论：我们的数据表明，感觉神经和新生血管在角膜中相互抑制。当血管生长被刺激时，神经消失，相反，去神经诱导血管生成。这种现象，在这里描述的眼睛，可能会对理解血管生成有深远的影响。(投资眼科VS科学。2013年；54：813-820)doi：10.1167/iovs.11-8379
PURPOSE. To evaluate the regulatory cross-talk of the vascular and neural networks in the cornea.METHODS. b-FGF micropellets (80 ng) were implanted in the temporal side of the cornea of healthy C57Bl/6 mice. On day 7, blood vessels (hemangiogenesis) and nerves were observed by immunofluorescence staining of corneal flat mounts. The next group of mice underwent either trigeminal stereotactic electrolysis (TSE), or sham operation, to ablate the ophthalmic branch of the trigeminal nerve. Blood vessel growth was detected by immunohistochemistry for PECAM-1 (CD31) following surgery. In another set of mice following TSE or sham operation, corneas were harvested for ELISA (VEGFR3 and pigment epithelium-derived factor [PEDF]) and for quantitative RT-PCR (VEGFR3, PEDF, and CD45). PEDF, VEGFR3, beta-3 tubulin, CD45, CD11b, and F4/80 expression in the cornea were evaluated using immunostaining.RESULTS. No nerves were detected in the areas subject to corneal neovascularization, whereas they persisted in the areas that were neovessel-free. Conversely, 7 days after denervation, significant angiogenesis was detected in the cornea, and this was associated with a significant decrease in VEGFR3 (57.5% reduction, P = 0.001) and PEDF protein expression (64% reduction, P < 0.001). Immunostaining also showed reduced expression of VEGFR3 in the corneal epithelial layer. Finally, an inflammatory cell infiltrate, including macrophages, was observed.CONCLUSION. Our data suggest that sensory nerves and neovessels inhibit each other in the cornea. When vessel growth is stimulated, nerves disappear and, conversely, denervation induces angiogenesis. This phenomenon, here described in the eye, may have far-reaching implications in understanding angiogenesis. (Invest Ophthalmol Vis Sci. 2013;54:813-820) DOI:10.1167/iovs.11-8379