The Role Of Infectious Pathogens In Ocular Disease

已知包括细菌、分枝杆菌、真菌、病毒和原生动物在内的感染性病原体可引起多种可识别的眼部感染，这些感染可在临床上诊断并用特异性抗生素治疗。典型的感染性眼部疾病的特征在于炎症反应，以清除宿主的侵入性微生物。有几种眼部疾病，包括肿瘤性、退行性和自身免疫性疾病，其中常规临床研究没有发现致病性感染病原体的直接证据。我们的研究小组有兴趣研究感染性病原体在眼部疾病发病机制中的作用，这可能会导致更好的诊断方法和治疗策略。在我们小组正在进行的临床研究中，通过跟踪一组主要患有成人T细胞白血病/淋巴瘤（ATL）和HTLV-1相关脊髓病/热带痉挛性下肢轻瘫（HAM/TSP）的非洲遗传HTLV-1感染患者，继续研究1型人T细胞嗜酸性病毒（HTLV-1）在人类眼部疾病发病机制中的作用。我们对这组患者的评估表明，遗传和环境因素可能会影响HTLV-1的眼部表现，因为临床结果似乎与HTLV-1感染流行的日本人群中已知的眼部结果显著不同。在过去的一年里，一种新的临床实体，严重急性呼吸系统综合征（SARS），被发现是由冠状病毒引起的。虽然SARS的主要临床表现是肺部，但据报道，受影响的患者也有眼部不适。我们有机会对8例SARS患者的9只眼进行了死后评估。组织学检查发现一对眼睛有轻度睫状体炎，一只眼睛有小的视神经出血，但光镜或电镜检查没有发现病毒感染的证据。由于冠状病毒可以在动物模型中诱导视网膜变性，因此已经提出了一种临床方案来确定SARS病原体（一种冠状病毒）是否可以诱导受影响患者的视网膜变化。幽门螺杆菌是一种革兰氏阴性菌，与胃炎、胃溃疡和十二指肠溃疡、胃腺癌和胃粘膜相关淋巴组织（MALT）淋巴瘤有关。报道称，H。幽门螺杆菌在包括青光眼和眼红斑痤疮在内的眼部疾病的发病机制中的作用。最近，我们发现了H。pylori基因在6/7例结膜MALT淋巴瘤患者的结膜中表达，表明细菌在这种肠外恶性肿瘤的发展中起直接作用。目前，我们正在制定血清流行病学研究，以调查H。葡萄膜炎和眼表疾病患者中的幽门螺杆菌。最后，我们还证明了存在组织胞浆菌荚膜DNA在一个固定的眼组织标本的脉络膜炎性浸润患者确认眼组织胞浆菌病的临床怀疑，否则将无法确诊。这些发现为开发更好的诊断工具和治疗与感染因子相关的眼部疾病提供了可能。

Infectious pathogens including bacteria, mycobacteria, fungi, viruses and protozoa are known to cause a wide variety of recognizable ocular infections that can be diagnosed clinically and treated with specific antibiotic therapy. Typically infectious ocular diseases are characterized by an inflammatory response to rid the host of the offending microorganism. There are several ocular conditions including neoplastic, degenerative and autoimmune diseases in which routine clinical investigations reveal no direct evidence of a causative infectious pathogen. Our group is interested in investigating the role of infectious pathogens in the pathogenesis of ocular diseases that may lead to better diagnostic methods and treatment strategies. In ongoing clinical studies in our group continue to investigate role of the Human T cell Lymphotrophic Virus, Type 1 (HTLV-1) in the pathogenesis of human ocular disease by following a cohort of HTLV-1 infected patients predominantly of African heritage with adult T-cell leukemia/lymphoma (ATL) and HTLV-1 associated myelopathy/Tropical spastic paraparesis (HAM/TSP). Our evaluations of this group of patients suggest that genetic and environmental factors may influence the ophthalmic manifestations of HTLV-1 as the clinical findings seem to differ significantly from the ocular finding known to occur in Japanese populations endemic for the HTLV-1 infection. Over the past year a new clinical entity, the severe acute respiratory syndrome (SARS), was found to be caused by a coronavirus. Although the primary clinical manifestation of SARS is pulmonary, ocular complaints have been reported in affected patients. We had an opportunity to evaluate 9 eyes of 8 patients with SARS postmortem. Histopathologic examination revealed mild cyclitis in one pair of eyes and small optic hemorrhage in one eye but no evidence of a viral infection could be demonstrated by light or electron microscopy. Because retinal degeneration could be induced by a coronavirus in an animal model, a clinical protocol has been proposed to determine if the SARS agent, a coronavirus, may induce retinal changes in affected patients. Helicobacter pylori is a gram negative bacteria which has been associated with gastritis, gastric and duodenal ulcers, gastric adenocarcinoma and gastric mucosa associated lymphoid tissue (MALT) lymphoma. Reports have implicated H. pylori in the pathogenesis of ocular disease including glaucoma and ocular rosacea. Recently we have identified H. pylori genes in the conjunctiva of 6/7 patients with conjunctival MALT lymphoma suggesting a direct role for the bacteria in the development of this extra-intestinal malignancy. Presently, we are formulating seroepidemiologic studies to investigate a possible role for H. pylori in patients with uveitis and ocular surface disease. Finally, we have also demonstrated the presence of Histoplasma capsulatum DNA in a fixed ocular tissue specimen of a patient with choroidal inflammatory infiltrates confirming the clinical suspicion of ocular histoplasmosis which would have otherwise not been diagnosed definitively. These findings offer the potential for the development of better diagnostic tools and treatments of ocular disease related to infectious agents.