Määttä Marko, Heljasvaara Ritva, Pihlajaniemi Taina, Uusitalo Marita
Department of Ophthalmology, Helsinki University Central Hospital, P.O. Box 220, 00029 Helsinki, HUS, Finland.
Graefes Arch Clin Exp Ophthalmol. 2007 Jan;245(1):74-81. doi: 10.1007/s00417-006-0281-y. Epub 2006 Apr 13.
The endostatin domain of type XVIII collagen (ColXVIII) inhibits neovascularization and regulates cell migration and matrix turnover. This study was designed to demonstrate the protein and gene expression patterns of ColXVIII/endostatin in the human eye and to ascertain whether endostatin is detectable in ocular fluid samples.
Twenty human eyes enucleated on account of choroidal melanoma were used for immunohistochemical stainings with antibodies against ColXVIII and endostatin. In situ hybridization was used to localize cells responsible for the production of mRNA for ColXVIII. Tear fluid, aqueous humor, and vitreous gel samples were used for Western immunoblotting to detect endostatin fragments in these samples.
ColXVIII was immunolocalized to almost all ocular structures, namely the basement membranes (BMs) of the corneal and conjunctival epithelia, Descement's membrane, the anterior border layer and posterior pigmented epithelium of the iris, the BMs of the pigmented and non-pigmented ciliary epithelia, the internal wall of Schlemm's canal and trabeculae, the ciliary and iris muscle cells, the BMs of the pigment epithelium of the retina, and the internal limiting membrane. Universal expression was seen in the BMs of vascular endothelial cells, and in fibroblasts located in the conjunctiva, the iris, and the ciliary body. Endostatin showed a corresponding pattern, but additional immunostaining was present in the corneal and conjunctival epithelial cells. Most epithelial and mesenchymal cells expressed the mRNA for ColXVIII. Endostatin-containing fragments varying in size were detected in tear fluid, aqueous humor and vitreous gel samples.
Practically all structures of the human eye contain ColXVIII/endostatin, emphasizing its possible important structural and functional role in the human eye. Furthermore, ocular fluid samples contain endostatin fragments, which may contribute to the antiangiogenic properties of the eye.
XVIII型胶原蛋白（ColXVIII）的内皮抑素结构域可抑制新血管形成，并调节细胞迁移和基质更新。本研究旨在展示ColXVIII/内皮抑素在人眼中的蛋白质和基因表达模式，并确定眼内液样本中是否可检测到内皮抑素。
选取20只因脉络膜黑色素瘤而摘除的人眼，用抗ColXVIII和内皮抑素的抗体进行免疫组织化学染色。采用原位杂交定位负责产生ColXVIII mRNA的细胞。采集泪液、房水和玻璃体凝胶样本，用于蛋白质免疫印迹法检测这些样本中的内皮抑素片段。
ColXVIII免疫定位至几乎所有眼内结构，即角膜和结膜上皮的基底膜、Descemet膜、虹膜的前边界层和后色素上皮、色素性和非色素性睫状体上皮的基底膜、小梁网和Schlemm管的内壁、睫状肌和虹膜肌细胞、视网膜色素上皮的基底膜以及内界膜。在血管内皮细胞的基底膜以及结膜、虹膜和睫状体中的成纤维细胞中均可见普遍表达。内皮抑素呈现相应模式，但在角膜和结膜上皮细胞中存在额外的免疫染色。大多数上皮细胞和间充质细胞表达ColXVIII的mRNA。在泪液、房水和玻璃体凝胶样本中检测到大小各异的含内皮抑素片段。
人眼的几乎所有结构均含有ColXVIII/内皮抑素，强调了其在人眼中可能具有的重要结构和功能作用。此外，眼内液样本含有内皮抑素片段，这可能有助于眼睛的抗血管生成特性。
