Baudouin Christophe, Liang Hong, Hamard Pascale, Riancho Luisa, Creuzot-Garcher Catherine, Warnet Jean-Michel, Brignole-Baudouin Françoise
Department of Ophthalmology, Quinze-Vingts National Ophthalmology Hospital and Ambroise Paré Hospital, APHP, Paris-Ouest School of Medicine, University of Versailles, Versailles, France.
Ophthalmology. 2008 Jan;115(1):109-15. doi: 10.1016/j.ophtha.2007.01.036. Epub 2007 May 29.
To investigate the expression of CCR5 and CCR4, two chemokine receptors, as markers of the T helper (Th) 1 and Th2 pathways, respectively, and class II antigen HLA-DR as a hallmark of inflammation on conjunctival cells obtained from patients receiving long-term glaucoma treatment.
Case-control study.
A total of 18 normal subjects and 70 glaucoma patients treated with topical antiglaucoma drugs for more than 1 year: 14 receiving a beta-blocker as monotherapy, 38 treated with a prostaglandin analog alone (19 with latanoprost, 6 with travoprost, 13 with bimatoprost), and 18 receiving multiple treatments.
Impression cytologic specimens (ICSs) were obtained from 1 eye of the patients and processed for flow cytometry. Conjunctival cells were extracted and incubated with monoclonal antibodies against CCR4, CCR5, HLA-DR, or their specific controls to measure, in a masked manner, the percentages of conjunctival cells positive for the 3 markers.
HLA-DR and chemokine receptors (CCR4 and CCR5) in ICSs.
Compared with all other groups, HLA-DR expression was raised significantly in the multitreatment group, whereas all monotherapies showed slight and nonsignificant increases. Both CCR4 and CCR5 were increased significantly in all 5 glaucoma groups compared with normal subjects, with no between-group differences.
This study demonstrates the overexpression of 2 chemokine receptors in the conjunctival epithelium of glaucoma patients treated over the long term. These results show the simultaneous overexpression of CCR4 and CCR5, suggesting that the chronic use of topical treatments may stimulate both the Th1 and Th2 systems simultaneously. These results also suggest that inflammatory mechanisms combining allergy with toxicity are at work and illustrate the complexity of inflammatory reactions occurring in the ocular surface of glaucoma patients.
研究两种趋化因子受体CCR5和CCR4的表达情况，它们分别作为辅助性T细胞（Th）1和Th2途径的标志物，以及II类抗原HLA - DR作为炎症标志，在接受长期青光眼治疗患者的结膜细胞中的表达情况。
病例对照研究。
总共18名正常受试者和70名接受局部抗青光眼药物治疗超过1年的青光眼患者：14名单独接受β受体阻滞剂治疗，38名仅接受前列腺素类似物治疗（19名接受拉坦前列素治疗，6名接受曲伏前列素治疗，13名接受比马前列素治疗），以及18名接受多种治疗。
从患者的一只眼睛获取印迹细胞学标本（ICSs），并进行流式细胞术处理。提取结膜细胞，与针对CCR4、CCR5、HLA - DR的单克隆抗体或其特异性对照进行孵育，以盲法测量这3种标志物阳性的结膜细胞百分比。
ICSs中的HLA - DR和趋化因子受体（CCR4和CCR5）。
与所有其他组相比，多药联合治疗组中HLA - DR表达显著升高，而所有单一疗法组均显示轻微且无显著增加。与正常受试者相比，所有5个青光眼组中CCR4和CCR5均显著增加，组间无差异。
本研究表明长期接受治疗的青光眼患者结膜上皮中两种趋化因子受体过表达。这些结果显示CCR4和CCR5同时过表达，提示局部治疗的长期使用可能同时刺激Th1和Th2系统。这些结果还表明过敏与毒性相结合的炎症机制在起作用，并说明了青光眼患者眼表发生的炎症反应的复杂性。
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