Abnormal maturation of the retinal vasculature in type XVIII collagen/endostatin deficient mice and changes in retinal glial cells due to lack of collagen types XV and XVIII
Abnormal maturation of the retinal vasculature in type XVIII collagen/endostatin deficient mice and changes in retinal glial cells due to lack of collagen types XV and XVIII
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DOI：
10.1096/fj.04-3101fje
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发表时间：
2005-06-01
期刊：
影响因子：
4.8
通讯作者：
Pihlajaniemi, T
中科院分区：
文献类型：
--
作者：
Hurskainen, M;Eklund, L;Pihlajaniemi, T
XVIII型胶原蛋白在视网膜血管发育的早期阶段和出生后玻璃体中原始血管的退化中是重要的。我们在这里显示，Col 18 a1（-/-）小鼠出生后第10天，由于持续性玻璃体血管系统的异常增生，视网膜血管变得密集。原位杂交显示正常的VEGF mRNA表达，但胶原蛋白XVIII缺陷小鼠的表型与仅表达VEGF（120）和VEGF（188）亚型的小鼠的表型非常相似，表明XVIII型胶原蛋白可能参与VEGF功能。研究发现，XVIII型胶原蛋白对于眼部血管生成是不可或缺的，而且Col 18 a1（-/-）小鼠中氧诱导的新血管形成强度也低于正常小鼠。我们观察到Col 18 a1（-/-）小鼠视网膜星形胶质细胞数量显著增加。野生型小鼠的视网膜血管被星形胶质细胞覆盖，退化的薄玻璃体血管缺乏星形胶质细胞，而Col 18 a1（-/-）小鼠的视网膜血管同样被星形胶质细胞覆盖，但玻璃体中的持久玻璃体血管没有。有趣的是，缺乏XVIII型胶原及其同源物XV型胶原的双无效小鼠具有由星形胶质细胞覆盖的持久性玻璃体血管，包括位于玻璃体中的部分。因此，我们假设XV型胶原蛋白是血管周围神经胶质细胞募集的调节因子，而XVIII型胶原蛋白调节其增殖。
Type XVIII collagen is important in the early phase of retinal vascular development and for the regression of the primary vasculature in the vitreous body after birth. We show here that the retina in Col18a1(-/-) mice becomes densely vascularized by anomalous anastomoses from the persistent hyaloid vasculature by day 10 after birth. In situ hybridizations revealed normal VEGF mRNA expression, but the phenotype of collagen XVIII deficient mice closely resembled that of mice expressing VEGF(120) and VEGF(188) isoforms only, suggesting that type XVIII collagen may be involved in VEGF function. Type XVIII collagen was found to be indispensable for angiogenesis in the eye, as also oxygen-induced neovascularization was less intense than normal in the Col18a1(-/-) mice. We observed a marked increase in the amount of retinal astrocytes in the Col18a1(-/-) mice. Whereas the retinal vessels of wild-type mice are covered by astrocytes and the regressing, thin hyaloid vessels are devoid of astrocytes, the retinal vessels in the Col18a1(-/-) mice were similarly covered by astrocytes but not the persistent hyaloid vessels in the vitreous body. Interestingly, double null mice lacking type XVIII collagen and its homologue type XV collagen had the persistent hyaloid vessels covered by astrocytes, including the parts located in the vitreous body. We thus hypothesize that type XV collagen is a regulator of glial cell recruitment around vessels and that type XVIII collagen regulates their proliferation.