Growth factor localization in choroidal neovascular membranes of age-related macular degeneration.
Growth factor localization in choroidal neovascular membranes of age-related macular degeneration.
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发表时间：
1994-07
影响因子：
4.4
通讯作者：
R. Amin;J. Puklin;R. Frank
中科院分区：
文献类型：
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作者：
R. Amin;J. Puklin;R. Frank
目的由于已知多种多肽生长因子会影响毛细血管内皮细胞有丝分裂，因此作者研究了通过手术从患有年龄相关性黄斑变性（ARMD）的人类受试者身上摘除的脉络膜新生血管膜（CNVM）中是否存在其中一些分子。方法 作者对 9 名 ARMD 受试者和一名死后眼睛进行研究的 ARMD 受试者手术切除的黄斑下 CNVM 进行了免疫电子显微镜研究。这些数据与来自八名正常受试者的视网膜色素上皮（RPE）和脉络膜组织进行了比较，这些正常受试者的眼睛是在死后接受的，另一名是在严重外伤后接受的。结果 来自 CNVM 的 RPE 细胞对酸性和碱性成纤维细胞生长因子（aFGF 和 bFGF）以及转化生长因子 β（TGF β）具有强烈的免疫反应性。一些免疫反应性是胞质内的，但大多数是溶酶体内的。此外，这些 CNVM 中靠近 RPE 层的一些绒毛膜毛细血管内皮细胞对 bFGF 和 FGF 受体呈免疫阳性。这两种物质的反应产物沿着细胞的腔前侧和腔侧的内皮质膜以规则的间隔分布，表明生长因子与其受体之间存在生理反应。基质深处的绒毛膜毛细血管内皮细胞对 bFGF 和 FGF 受体抗体没有反应。正常眼的 RPE 或脉络膜毛细血管内皮细胞中的生长因子几乎没有免疫反应性。 aFGF和bFGF免疫反应性具有高度特异性，因为当抗体与10(-6) M aFGF而不是与相同浓度的bFGF一起孵育时，aFGF阳性被消除，而bFGF免疫反应性通过抗体与bFGF而不是与aFGF一起孵育而被消除。来自正常眼和受ARMD影响的眼的RPE细胞对细胞质视黄醛结合蛋白和超氧化物歧化酶的抗体表现出强的细胞质免疫反应性，而对波形蛋白的抗体表现出弱的反应性。结论 这些结果与一种或两种 FGF 与脉络膜新生血管形成因果关系的假设一致。作者报告了红氪激光光凝后色素大鼠实验性脉络膜新生血管形成的类似观察结果。 TGF beta 可能有助于调节这些有丝分裂原的作用。作者认为，物理或化学损伤后，RPE 细胞会诱导生长因子产生。由于这些细胞受到损伤，尽管编码 FGF 产生的 DNA 中不存在“信号序列”，但 FGF 分子仍然可以从细胞中释放出来。
PURPOSE Because several polypeptide growth factors are known to influence capillary endothelial cell mitogenesis, the authors investigated the presence of some of these molecules in choroidal neovascular membranes (CNVMs) removed surgically from human subjects with age-related macular degeneration (ARMD). METHODS The authors performed immunoelectron microscopic studies on surgically removed submacular CNVMs from nine subjects with ARMD and from one subject with ARMD whose eye was studied after death. These were compared with retinal pigment epithelial (RPE) and choroidal tissue from eight normal subjects whose eyes were received after death and one received after massive trauma. RESULTS RPE cells from the CNVMs were strongly immunoreactive for acidic and basic fibroblast growth factor (aFGF and bFGF) and for transforming growth factor beta (TGF beta). Some of the immunoreactivity was intracytoplasmic, but most was intralysosomal. In addition, some choriocapillary endothelial cells located close to the RPE layer in these CNVMs were immunopositive for bFGF and for FGF receptor. Reaction product for these two substances was located at regular intervals along the endothelial plasma membrane on both the anteluminal and the luminal side of the cells, suggesting a physiological reaction between the growth factor and its receptor. Choriocapillary endothelial cells deeper within the stroma were unreactive to bFGF and FGF receptor antibodies. There was little immunoreactivity for the growth factors in RPE or choriocapillary endothelial cells from normal eyes. The aFGF and bFGF immunoreactivity was highly specific because aFGF positivity was abolished when the antibody was incubated with 10(-6) M aFGF but not a with the same concentration of bFGF, whereas bFGF immunoreactivity was abolished by incubation of the antibody with bFGF but not with aFGF. RPE cells from normal eyes and from eyes affected by ARMD showed strong cytoplasmic immunoreactivity to antibodies for cytoplasmic retinaldehyde-binding protein and superoxide dismutase and weak reactivity to antibodies for vimentin. CONCLUSIONS These results are consistent with the hypothesis that one or both FGFs are causally related to the development of choroidal neovascularization. The authors have reported similar observations in experimental choroidal neovascularization in pigmented rats after red krypton laser photocoagulation. TGF beta may serve to modulate the effects of these mitogens. The authors suggest that growth factor production is induced in RPE cells after physical or chemical damage. Because of the damage to these cells, FGF molecules can be released from the cells despite the absence of a "signal sequence" in the DNA coding for FGF production.