Role Of Infectious Pathogens In Ocular

众所周知，包括细菌、分枝杆菌、真菌、病毒和原虫在内的感染性病原体可引起各种可识别的眼部感染，这些感染可以在临床上诊断并使用特定的抗生素治疗。典型的感染性眼病以炎性反应为特征，以清除宿主中的有害微生物。有几种眼部疾病，包括肿瘤性、退行性和自身免疫性疾病，常规临床检查显示没有直接证据表明是致病的感染性病原体。我们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。在一项临床研究中，我们小组的成员首次描述了与免疫球蛋白水平升高有关的角膜病变的存在，以及感染了人类T细胞淋巴病毒(HTLV-1)的牙买加患者，这种病毒已被认为会导致葡萄膜炎。通过对其中一例患者的结膜标本进行显微解剖和聚合酶链式反应，我们首次鉴定了一例结膜成人T细胞白血病/淋巴瘤患者的HTLV-1基因和T细胞受体基因重排。由于这些发现，已计划进行临床研究，以进一步确定生活在牙买加的患者中与HTLV-1有关的眼部疾病的范围，并确定病毒感染导致眼睛并发症的机制。在使用类似技术的其他实验室研究中，我们已经证明存在一种病毒病原体，HPV33型，在艾滋病患者的良性结膜乳头状瘤中，这种病毒以前不会导致人类眼部疾病。此外，我们还在少数免疫功能正常的原发性眼内淋巴瘤患者的恶性淋巴细胞中发现了弓形虫DNA序列的证据。这些发现意义重大，因为它们表明了眼睛中感染性物质的致癌潜力，并提高了良性和恶性形式的眼部肿瘤疾病都可能通过抗生素治疗来预防或治疗的可能性。最后，通过对人类弓形虫病的实验小鼠模型的研究，我们表明，在实验感染弓形虫包囊的小鼠没有细胞凋亡(程序性细胞死亡)的情况下，细胞因子对感染具有保护作用。这一数据令人兴奋，因为它表明细胞因子可能被用于治疗人类感染性眼病。

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 a clinical study members of our group have described for the first time the presence of corneal lesions associated with elevated immunoglobulin levels and in Jamaican patients infected with the human T-cell lymphotropic virus (HTLV-1) which was already known to cause uveitis. Using microdissection and PCR on a conjunctival specimen removed from one of these patients we have identified for the first time HTLV-1 genes and rearrangements of the T-cell receptor gene in a patient with conjunctival adult T-cell leukemia/lymphoma. As result of these findings clinical studies have been planned to further define the spectrum of ocular disease associated with HTLV-1 in patients living in Jamaica and to determine the mechanism by which the viral infection causes the ocular complications. In other laboratory studies using a similar technique we have demonstrated the presence of a viral pathogen, HPV type 33, not previously known to cause human ocular disease in a benign conjunctival papilloma in a patient with AIDS. Additionally, we have found evidence of toxoplasma DNA sequences in the malignant lymphoid cells in a few immunocompetent patients with primary intraocular lymphoma. These findings are significant because they suggest the oncogenic potential of infectious agents in the eye and raise the possibility that both benign and malignant forms of neoplastic ocular diseases can possibly be prevented or treated by antibiotic therapy. Finally, working with an experimental murine model of human toxoplasmosis we showed that in the absence of apoptosis (programmed cell death) in mice experimentally infected with toxoplasma cysts, cytokines are protective against the infection. This data is exciting because it suggests cytokines may be used therapeutically to treat infectious ocular disease in humans.