The Role Of Infectious Pathogens In Ocular Disease

已知感染性病原体包括细菌、分枝杆菌、真菌、病毒和原生动物，可引起各种可识别的眼部感染，这些感染可在临床上诊断并通过特定的抗生素治疗进行治疗。典型的感染性眼病的特点是炎症反应，以摆脱宿主的致病微生物。有几种眼病，包括肿瘤、退行性和自身免疫性疾病，常规临床调查显示没有直接证据表明有传染性病原体。我们的小组对研究感染性病原体在眼部疾病发病机制中的作用感兴趣，这可能会导致更好的诊断方法和治疗策略。在正在进行的临床研究中，我们小组通过跟踪一组HTLV-1感染的主要为非洲血统的成人T细胞白血病/淋巴瘤（ATL）和HTLV-1相关脊髓病/热带痉挛性截瘫（HAM/TSP）患者，继续研究HTLV-1型人T细胞淋巴营养病毒（HTLV-1）在人类眼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影响HTLV-1的眼部表现，因为临床表现似乎与日本HTLV-1感染流行人群中已知的眼部表现有很大不同。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，但也有患者出现眼部症状的报道。我们有机会对8名SARS患者的9只眼睛进行尸检。组织病理学检查显示一副眼睛轻度环状炎，一只眼睛小视神经出血，但光镜或电子显微镜未见病毒感染的证据。由于在动物模型中，冠状病毒可以诱导视网膜变性，因此提出了一种临床方案，以确定SARS病原体（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、胃和十二指肠溃疡、胃腺癌和胃黏膜相关淋巴组织（MALT）淋巴瘤有关。有报道表明幽门螺杆菌与包括青光眼和眼红斑痤疮在内的眼部疾病的发病机制有关。最近，我们在6/7例结膜MALT淋巴瘤患者的结膜中发现了幽门螺杆菌基因，提示该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，以调查幽门螺旋杆菌在葡萄膜炎和眼表疾病患者中的可能作用。最后，我们还证明了在脉络膜炎症浸润患者的固定眼组织标本中存在荚膜组织浆体DNA，证实了眼组织浆体病的临床怀疑，否则将无法确诊。这些发现为开发与感染因子相关的眼科疾病的更好的诊断工具和治疗方法提供了潜力。

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.