Di Girolamo Nick, Kumar Rakesh K, Coroneo Minas T, Wakefield Denis
Inflammation Research Unit, School of Medical Sciences, Department of Pathology, Faculty of Medicine, University of New South Wales, Sydney, Australia.
Invest Ophthalmol Vis Sci. 2002 Nov;43(11):3430-7.
Pterygia are common ocular surface lesions that are thought to be induced by exposure to ultraviolet (UV) radiation. The hypothesis tested in the current study is that UV radiation modulates the expression of interleukin (IL)-6 and -8, which could promote the neovascularization and chronic inflammation regularly observed in pterygia.
Immunohistochemical analysis was performed on 10 pterygia and 14 specimens of normal conjunctiva (4 of which contained limbus), to identify the cellular source of these cytokines. Pterygium epithelial cells were exposed to UVB (0-100 mJ/cm(2)) and the expression of cytokine mRNA and protein was determined by reverse transcription-polymerase chain reaction (RT-PCR), RNase protection assay (RPA), and enzyme immunoassay. Similarly, pterygium tissue in organ culture was UVB irradiated and the supernatants analyzed for cytokine production.
IL-6 and -8 proteins were abundantly expressed, predominantly by the pterygium epithelium, with additional IL-8 immunoreactivity associated with the vascular endothelium. In contrast, significantly less staining for both cytokines was observed in normal conjunctiva, cornea, and limbus. Expression of both IL-6 and -8 mRNA and protein was induced in UVB-irradiated pterygium epithelial cells in a time- and dose-dependent manner. Similarly, IL-6 and -8 proteins were significantly elevated in UVB-treated compared with nonirradiated pterygia.
This study provides the first direct experimental evidence that implicates UV in the pathogenesis of pterygia. The two proinflammatory cytokines that are induced by UV radiation may play a key role in the development of pterygia, by initiating blood vessel formation, cellular proliferation, tissue invasion, and inflammation. Strategies aimed at reducing ocular exposure to UV light may decrease the incidence and recurrence of pterygia.
翼状胬肉是常见的眼表病变，被认为是由紫外线（UV）辐射诱发的。本研究检验的假设是，紫外线辐射可调节白细胞介素（IL）-6和-8的表达，这可能促进翼状胬肉中常见的新生血管形成和慢性炎症。
对10例翼状胬肉和14例正常结膜标本（其中4例含角膜缘）进行免疫组织化学分析，以确定这些细胞因子的细胞来源。将翼状胬肉上皮细胞暴露于中波紫外线（UVB）（0 - 100 mJ/cm²），通过逆转录聚合酶链反应（RT-PCR）、核糖核酸酶保护分析（RPA）和酶免疫测定法测定细胞因子mRNA和蛋白的表达。同样，对器官培养中的翼状胬肉组织进行UVB照射，并分析上清液中的细胞因子产生情况。
IL-6和-8蛋白大量表达，主要由翼状胬肉上皮表达，另外IL-8免疫反应性与血管内皮相关。相比之下，在正常结膜、角膜和角膜缘中观察到这两种细胞因子的染色明显较少。UVB照射的翼状胬肉上皮细胞中IL-6和-8 mRNA及蛋白的表达呈时间和剂量依赖性诱导。同样，与未照射的翼状胬肉相比，UVB处理的翼状胬肉中IL-6和-8蛋白显著升高。
本研究提供了首个直接实验证据，表明紫外线与翼状胬肉的发病机制有关。紫外线辐射诱导的两种促炎细胞因子可能通过启动血管形成、细胞增殖、组织侵袭和炎症，在翼状胬肉的发展中起关键作用。旨在减少眼部紫外线暴露的策略可能会降低翼状胬肉的发病率和复发率。
