Hepatocyte growth factor and its role in the pathogenesis of retinal detachment.
Hepatocyte growth factor and its role in the pathogenesis of retinal detachment.
复制标题
DOI：
10.1167/iovs.03-0355
复制
发表时间：
2004
影响因子：
4.4
通讯作者：
M. Jin;You-xin Chen;Shi-kun He;S. Ryan;D. Hinton
中科院分区：
文献类型：
--
作者：
M. Jin;You-xin Chen;Shi-kun He;S. Ryan;D. Hinton
目的：肝细胞生长因子（HGF）调节视网膜色素上皮（RPE）细胞的屏障功能。本研究的目的是确定HGF在RPE中的过度表达是否会诱导视网膜脱离（RD）。方法E1/ e3缺失腺病毒载体编码HGF （Ad CMV）。HGF)，绿色荧光蛋白（Ad CMV）。GFP)或结缔组织生长因子（AdCMV.CTGF）在成年色素兔（5 × 10(4)斑块形成单位[pfu]/眼）视网膜下注射。通过眼底摄影观察动物长达28天。采用免疫组化、ELISA法检测视网膜和玻璃体中HGF的表达。光镜和电镜下进行组织病理学检查。结果对照眼注射AdCMV。GFP几乎只在RPE单层中表达。眼睛注射AdCMV。HGF在注射部位的RPE细胞中表现出较强的免疫阳性。玻璃体中HGF水平升高在注射后第7天达到峰值，注射后第28天降至基线。眼睛注射AdCMV。在HGF表达的时间框架内，HGF在脉络膜发生慢性RD和慢性炎症。视网膜下间隙可见成组增殖的RPE细胞，在某些情况下形成多层细胞膜。注射AdCMV后，眼内未见RD和微小的形态学改变。GFP或AdCMV.CTGF。结论：HGF在RPE中过表达可诱导慢性、浆液性RD伴RPE视网膜下增生。这项工作为RD的发病机制提供了新的思路，并提示HGF作为RD治疗干预的靶点应进一步研究。
PURPOSE Hepatocyte growth factor (HGF) regulates barrier function of retinal pigment epithelial (RPE) cells. The purpose of this study was to determine whether overexpression of HGF in the RPE induces retinal detachment (RD). METHODS E1/E3-deleted adenoviral vectors encoding HGF (Ad CMV.HGF), green fluorescent protein (Ad CMV.GFP), or connective tissue growth factor (AdCMV.CTGF) were injected subretinally in adult pigmented rabbits (5 x 10(4) plaque-forming units [pfu]/eye). Animals were observed for up to 28 days with fundus photography. HGF expression in the retina and vitreous was determined using immunohistochemistry, and ELISA. Histopathologic examinations were performed with light and electron microscopy. RESULTS Control eyes injected with AdCMV.GFP showed GFP expression almost exclusively in the RPE monolayer. Eyes injected with AdCMV.HGF showed strong HGF immunopositivity in RPE cells at the injection site. Elevated HGF levels were found in the vitreous peaking at postinjection day 7, diminishing to baseline by postinjection day 28. Eyes injected with AdCMV.HGF developed chronic RD and chronic inflammation in the choroid within the time frame of HGF expression. Groups of proliferating RPE cells were seen in the subretinal space in the region of the RD, and in some cases multilayered cellular membranes developed. No RD and minimal morphologic changes were seen in the eyes injected with AdCMV.GFP or AdCMV.CTGF. CONCLUSIONS Overexpression of HGF in RPE induces chronic, serous RD with subretinal proliferation of RPE. This work provides insight into the pathogenesis of RD and suggests that HGF should be further investigated as a target for therapeutic intervention in RD.