Animal models of dry eye: A critical assessment of opportunities and limitations
Animal models of dry eye: A critical assessment of opportunities and limitations
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DOI：
10.1167/iovs.03-1055
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发表时间：
2004-06-01
影响因子：
4.4
通讯作者：
Dana, MR
中科院分区：
文献类型：
--
作者：
Barabino, S;Dana, MR
干眼症，或干性角膜结膜炎(KCS)，影响着全球数千万人，是最常见的眼病之一。1国家眼科研究所干眼临床试验工业研讨会提出了一项分类，基本上将干眼综合征分为两种主要类型：泪液缺乏型(包括SJÖGREN‘s综合征和非SJÖGREN’s泪液缺乏)和蒸发型。2近年来，干眼症的免疫发病机制是复杂的、多因素的。SJÖGren‘s综合征是与KCS相关的外分泌缺乏的经典形式，其特征是泪腺和唾液腺的慢性炎性浸润。主要的细胞类型是CD4+T细胞，这些细胞似乎在Fas介导的凋亡方面存在缺陷，从而使其渗透到外分泌组织中受到损害。然而，究竟是什么因素刺激了T细胞对腺体的侵袭，目前尚不清楚。最近，泪腺腺泡细胞可能表达第二类主要组织相容性复合体(MHC)分子、组织蛋白B和D，以及核糖核蛋白颗粒La/SSB蛋白，这一发现为这些细胞可能参与自身抗原的异常递送，从而有可能启动自身反应性T细胞提供了一些支持(但没有确凿证据)。4干眼的发病机制并不局限于泪液炎症。事实上，神经元对泪液分泌刺激的中断，跨膜和分泌性粘蛋白表达的缺陷，以及眉板腺功能障碍，都可以导致各种形式的KCS。2大量的动物模型被用来反映KCS涉及的多种病理生理机制。了解这些不同干眼模型的独特特征及其局限性，将有助于更好地了解它们在机械和治疗性研究设计中的应用。
Dry eye syndrome, or keratoconjunctivitis sicca (KCS), affects tens of millions of people worldwide, representing one of the most common ocular diseases. 1 The National Eye Institute Industry Workshop on Clinical Trials in Dry Eyes produced a classification that essentially separates dry eye syndrome into two major types: tear-deficient forms (including Sjögren’s syndrome and non-Sjögren’s tear-deficient) and evaporative forms. 2 Recently, it has become clear that the immunopathogenesis of dry eye is complex and multifactorial. Sjögren’s syndrome, which is the classic form of exocrine deficiency associated with KCS, is characterized by a chronic inflammatory infiltration of the lacrimal and salivary glands. The predominant cell type is CD4+ T cells that appear to have a defect in Fas-mediated apoptosis, thereby rendering their infiltration into exocrine tissue damaging. 3 However, exactly what factors incite the infiltration of glands by T cells remains unknown. Recently, the observation that lacrimal gland acinar cells may express class II major histocompatibility complex (MHC) molecules, cathepsins B and D, and ribonucleoprotein particle La/SSB proteins has provided some support (but no definitive proof) for the thesis that these cells may be involved in aberrant presentation of autoantigens, thereby potentially capable of priming autoreactive T cells. 4But the pathogenic mechanisms in dry eye are not limited to those involved in lacrimal inflammation. Indeed, interruption of neuronal stimulation for tear secretion, defects in transmembrane and secretory mucin expression, and Meibomian gland dysfunction can all lead to various forms of KCS. 2 Numerous animal models have been developed to reflect the multiplicity of pathophysiologic mechanisms involved in KCS. Understanding the unique characteristics of these different models of dry eye, and their limitations, will provide a better insight into their use in mechanistic and therapeutic study design.