Identification of Chlamydia pneumoniae within human choroidal neovascular membranes secondary to age-related macular degeneration
Identification of Chlamydia pneumoniae within human choroidal neovascular membranes secondary to age-related macular degeneration
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DOI：
10.1007/s00417-005-1169-y
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发表时间：
2005-11-01
影响因子：
2.7
通讯作者：
Miller, JW
中科院分区：
文献类型：
--
作者：
Kalayoglu, MV;Bula, D;Miller, JW
视网膜相关性黄斑变性（AMD）是美国失明的主要原因，越来越多的证据表明它是一种炎症性疾病。原核专性细胞内病原体肺炎衣原体正在成为心血管疾病的一个新的危险因素，最近的血清流行病学数据表明，肺炎衣原体感染也与AMD有关。在这项研究中，我们检测了新生血管性AMD患者的脉络膜新生血管膜（CNV）组织中是否存在C。肺炎，并确定病原体是否可以导致新生血管性AMD的方式失调的关键细胞类型的功能。对9例新生血管性AMD患者的CNV进行了C。通过免疫组化（IHC）和聚合酶链反应（PCR）检测肺炎;此外，我们对9只非AMD眼睛进行PCR，并对5只非AMD CNV，7只非AMD眼睛和1只内界膜标本进行IHC。最后，将人单核细胞衍生的巨噬细胞和视网膜色素上皮（RPE）细胞暴露于C。pneumoniae）中，并在体外测定促血管生成免疫调节剂（VEGF、IL-8和MCP-1）的产生。免疫组化法检测到9例AMD CNV中的4例，PCR法检测到9例AMD CNV中的2例，肺炎衣原体诱导人巨噬细胞产生VEGF，并增加RPE细胞产生IL-8和MCP-1。相比之下，22个非AMD标本中没有一个显示出C。肺炎。这些数据表明，能够诱导慢性炎症和促血管生成细胞因子的病原体可以在一些AMD CNV中检测到，并表明感染可能有助于AMD的发病机制。CNV、7只非AMD眼和1只内界膜标本。最后，将人单核细胞衍生的巨噬细胞和视网膜色素上皮（RPE）细胞暴露于C。pneumoniae）中，并在体外测定促血管生成免疫调节剂（VEGF、IL-8和MCP-1）的产生。免疫组化法检测到9例AMD CNV中的4例，PCR法检测到9例AMD CNV中的2例，肺炎衣原体诱导人巨噬细胞产生VEGF，并增加RPE细胞产生IL-8和MCP-1。相比之下，22个非AMD标本中没有一个显示出C。肺炎。这些数据表明，能够诱导慢性炎症和促血管生成细胞因子的病原体可以在一些AMD CNV中检测到，并表明感染可能有助于AMD的发病机制。
Age-related macular degeneration (AMD) is a leading cause of blindness in the United States, and increasing evidence suggests that it is an inflammatory disease. The prokaryotic obligate intracellular pathogen Chlamydia pneumoniae is emerging as a novel risk factor in cardiovascular disease, and recent sero-epidemiological data suggest that C pneumoniae infection is also associated with AMD. In this study, we examined choroidal neovascular membrane (CNV) tissue from patients with neovascular AMD for the presence of C. pneumoniae and determined whether the pathogen can dysregulate the function of key cell types in ways that can cause neovascular AMD. Nine CNV removed from patients with neovascular AMD were examined for the presence of C. pneumoniae by immunohistochemistry (IHC) and polymerase chain reaction (PCR); in addition, we performed PCR on nine non-AMD eyes, and IHC on five non-AMD CNV, seven non-AMD eyes, and one internal limiting membrane specimen. Finally, human monocyte-derived macrophages and retinal pigment epithelial (RPE) cells were exposed to C. pneumoniae and assayed in vitro for the production of pro-angiogenic immunomodulators (VEGF, IL-8, and MCP-1). C pneumoniae was detected in four of nine AMD CNV by IHC and two of nine AMD CNV by PCR, induced VEGF production by human macrophages, and increased production of IL-8 and MCP-1 by RPE cells. In contrast, none of the 22 non-AMD specimens showed evidence for C. pneumoniae. These data indicate that a pathogen capable of inducing chronic inflammation and pro-angiogenic cytokines can be detected in some AMD CNV, and suggest that infection may contribute to the pathogenesis of AMD. CNV, seven non-AMD eyes, and one internal limiting membrane specimen. Finally, human monocyte-derived macrophages and retinal pigment epithelial (RPE) cells were exposed to C. pneumoniae and assayed in vitro for the production of pro-angiogenic immunomodulators (VEGF, IL-8, and MCP-1). C pneumoniae was detected in four of nine AMD CNV by IHC and two of nine AMD CNV by PCR, induced VEGF production by human macrophages, and increased production of IL-8 and MCP-1 by RPE cells. In contrast, none of the 22 non-AMD specimens showed evidence for C. pneumoniae. These data indicate that a pathogen capable of inducing chronic inflammation and pro-angiogenic cytokines can be detected in some AMD CNV, and suggest that infection may contribute to the pathogenesis of AMD.