抗肿瘤坏死因子制剂与葡萄膜炎

肿瘤坏死因子(TNF )与葡萄膜炎的发生发展密切相关,成为免疫抑制治疗的靶点,抗TNF生物制剂应用于临床,可望超越常规药物的疗效,并可避免严重副作用。本文就目前该类药物的制剂类型、作用机制、疗效、副作用的基础和临床研究进展作一综述。     

葡萄膜炎的生物治疗进展

葡萄膜炎多发于青壮年,多为自身免疫性疾病,常反复发作。研究表明,生物制剂可以干扰机体内引起炎症反应过程的具有特定分子或途径,在葡萄膜炎的发病过程中发挥了关键的治疗作用,以达到治疗葡萄膜炎的目的。本文意在探讨抗肿瘤坏死因子制剂、白细胞介素受体拮抗剂、干扰素、抗淋巴细胞特异性抑制剂等生物制剂在葡萄膜炎治疗过程中的治疗进展。     

抗肿瘤坏死因子制剂与葡萄膜炎

肿瘤坏死因子(TNF)与葡萄膜炎的发生发展密切相关，成为免疫抑制治疗的靶点，抗TNF生物制剂应用于临床，可望超越常规药物的疗效，并可避免严重副作用。本就目前该类药物的制剂类型、作用机制、疗效、副作用的基础和临床研究进展作一综述。     

重视葡萄膜炎药物治疗研究,提高葡萄膜炎药物治疗效果

各类非感染性葡萄膜炎的治疗,糖皮质激素是首选药物.但单一药物治疗对慢性或复发性葡萄膜炎的疗效欠佳,长期应用又具有明显的毒副作用,因此部分患者需辅助以免疫抑制剂或生物制剂治疗.不同类型免疫抑制剂和生物制剂的作用机制不完全相同,因此各自的适应证、疗效和毒副作用也不尽一样.在临床实践中,应根据葡萄膜炎的类型选择敏感的免疫抑制剂或生物制剂治疗,同时密切观察其疗效和毒副作用.葡萄膜炎治疗中的常用药物类型、疗效以及存在的问题值得我们进一步关注和深入研究,以提高葡萄膜炎药物治疗的效果.     

大鼠角膜移植排斥反应血清肿瘤坏死因子—α测定

本研究利用大鼠角膜移植的动物模型 ,检测外周血清中肿瘤坏死因子 α(ｔｕｍｏｒｎｅｃｒｏｓｉｓｆａｃｔｏｒ α ,ＴＮＦ α)水平 ,并观察应用抗ＴＮＦ α单克隆抗体治疗后上述指标的变化 ,以探讨ＴＮＦ α在角膜移植免疫排斥反应中的作用。1　材料与方法采用近交系大鼠Ｆ344(ＲＴｌｅ) 15只和Ｌｏｕ(ＲＴｌｙ) 5 5只 ,雄性 ,体重 2 0 0～ 2 5 0ｇ ,约 2月龄 ,购自中国医学科学院医学实验动物研究所。以Ｌｏｕ大鼠为受体 ,随机分为 4组。Ａ组 :正常对照组 (ｎ =4) ,Ｂ组 :同基因移植组 (Ｌｏｕ→Ｌｏｕ ,ｎ =14 ) ,Ｃ组 :异基因移植组 (…     

肿瘤坏死因子对晶状体上皮细胞原癌基因表达的作用

目的研究肿瘤坏死因子α （ＴＮ－α）对体外培养的牛眼晶状体上皮细胞中原癌基因 ｆｏｓ，ｊｕｎ， ｍｙｂ， ｍｙｃ， ｒａｓ等蛋白产物表达的作用。方法细胞经 １０ Ｕ／ｍｌ ＴＮＦ－α作用不同时间后，采用卵白素－生物素－过氧化物酶复合物（ＡＢＣ）免疫酶标技术测定蛋白表达。结果经ＴＮＦ－α作用后，几种原癌基因表达的阳性细胞百分率均明显增高（Ｐ＜０．０１）。 ｆｏｓ，ｊｕｎ，ｍｙｂ，ｒａｓ在刺激１ｈ后即达到顶峰，ｍｙｃ在刺激２ｈ后达到顶峰，随后很快下降，恢复至正常水平。同时，细胞的阳性反应强度增加，细胞核内变化更为明显。结论ＴＮＦ－α通过激活细胞内原癌基因的表达而促进晶状体上皮细胞的增殖。     

葡萄膜炎的治疗进展

葡萄膜炎是一类常见眼科致盲疾病,其发病机制尚未完全阐明,涉及感染、自身免疫等多种机制.目前葡萄膜炎的治疗仍主要依靠类固醇激素、免疫抑制剂等药物,但副反应普遍较大,限制了在临床上的应用.随着分子生物学的进展,一些新型生物制剂药物也用于治疗葡萄膜炎;基因治疗、RNA干扰等技术也将逐步用于葡萄膜炎的治疗.文中拟对当前葡萄膜炎的治疗进展作一综述.     

人工合成白细胞介素-1受体阻断剂对大鼠葡萄膜炎的影响

目的 观察人工合成的白细胞介素－１受体阻断剂对大鼠葡萄膜炎的治疗作用。方法 选择１８只（３６只眼）Ｓｐｒａｇｕｅ＝Ｄａｗｌｅｙ大鼠,采用酶联免疫吸附测定的方法,对人工合成的ＩＬ－１受体阻断剂治疗前、后的大鼠葡萄膜炎动物模型的视网膜内ＩＬ－β和肿瘤坏死因子的含量进行测定。结果 ＩＬ－１受体阻断剂（ＣＫ－１３８,ＣＫ－１３９）治疗组,基 膜内ＩＬ－１β和ＴＮＦα的含量均显著低于对照组的含量。结论 人工     

血清可溶性肿瘤坏死因子受体与2型糖尿病视网膜病变相关性研究

目的　研究血清可溶性肿瘤坏死因子受体（ｓｏｌｕｂｌｅｔｕｍｏｒｎｅｃｒｏｓｉｓｆａｃｔｏｒｒｅｃｅｐｔｏｒ,ｓＴＮＦＲ）与２型糖尿病视网膜病变的相关性。方法　６６例２型糖尿病患者通过眼底检查和眼底荧光血管造影按照ＥＤＴＲＳ分期分为３组:无糖尿病视网膜病变（ｎｏｄｉａｂｅｔｉｃｒｅｔｉｎｏｐａｔｈｙ,ＮＤＲ;ｎ＝２２）组、非增殖型糖尿病视网膜病变（ｎｏｎｐｒｏｌｉｆｅｒａｔｉｖｅｄｉａｂｅｔｉｃｒｅｔｉｎｏｐａｔｈｙ,ＮＰＤＲ;ｎ＝２４）组和增殖型糖尿病视网膜病变（ｐｒｏｌｉｆｅｒａｔｉｖｅｄｉａｂｅｔｉｃｒｅｔｉｎｏｐａｔｈｙ,ＰＤＲ;ｎ＝２０）组。２１名健康人作为对照组。检测４组研究对象血清中肿瘤坏死因子（ｔｕｍｏｒｎｅｃｒｏｓｉｓｆａｃｔｏｒ,ＴＮＦ）-α、ｓＴＮＦＲ-１、ｓＴＮＦＲ-２水平。组间统计分析采用非参数Ｍａｎｎ-ＷｈｉｔｎｅｙＵ检验。结果　血清中ＴＮＦ-α中位数分别为:对照组０ｐｇ·ｍＬ－１、ＮＤＲ组３．４５ｐｇ·ｍＬ－１、ＮＰＤＲ组３．９２ｐｇ·ｍＬ－１、ＰＤＲ组８．１２ｐｇ·ｍＬ－１。对照组与ＰＤＲ组（Ｐ＜０．００１）、ＮＤＲ组与ＰＤＲ组（Ｐ＝０．００８）比较差异均有统计学意义。血清中ｓＴＮＦＲ-１水平中位数:对照组１．５０ｎｇ·ｍＬ－１、ＮＤＲ组１．８８ｎｇ·ｍＬ－１、ＮＰＤＲ组２．５８ｎｇ·ｍＬ－１、ＰＤＲ组３．００ｎｇ·ｍＬ－１。对照组与ＮＰＤＲ组（Ｐ＜０．００１）、对照组与ＰＤＲ组（Ｐ＜０．００１）、ＮＤＲ组与ＮＰＤＲ组（Ｐ＝０．００７）、ＮＤＲ组与ＰＤＲ组（Ｐ＜０．００１）比较,差异均有统计学意义。血清中ｓＴ-ＮＦＲ-２中位数分别为:对照组３．８８ｎｇ·ｍＬ－１、ＮＤＲ组５．０１ｎｇ·ｍＬ－１、ＮＰＤＲ组５．２１ｎｇ·ｍＬ－１、ＰＤＲ组６．３３ｎｇ·ｍＬ－１。除了ＮＤＲ组与ＮＰＤＲ组（Ｐ＝０．０７０）间差异无统计学意义外,其他组间差异均有统计学意义（均为Ｐ＜０．０５）。结论　血清中ｓＴＮＦＲ与２型糖尿病视网膜病变密切相关,表明ｓＴＮＦＲ在糖尿病视网膜病变的发生发展中起到了一定的作用。对ｓＴＮＦＲ进行进一步研究可以寻找治疗糖尿病视网膜病变新的靶点。     

免疫抑制剂在顽固性葡萄膜炎治疗中的应用

糖皮质激素是治疗葡萄膜炎的首选药物,但长期应用具有明显的毒副作用,并且单一药物治疗对慢性或顽固性葡萄膜炎的疗效欠佳.选择性T细胞抑制剂、抗代谢药物、烷化剂、基因重组干扰素-α、抗肿瘤坏死因子单克隆抗体、中药类免疫调节剂等免疫抑制剂为顽固性葡萄膜炎的治疗提供了更加丰富的选择.由于不同类型免疫抑制剂的作用机制不同,各自适应证、疗效和毒副作用也不尽相同.在临床实践中,应根据葡萄膜炎的类型选择敏感的免疫抑制剂药物,同时密切观察其疗效和毒副作用.     

Biologic Therapy for HLA-B27-associated Ocular Disorders

The treatment of articular and extra-articular manifestations associated with HLA-B27 has undergone dramatic changes over the past two decades, mainly as a consequence of the introduction of biologic agents and in particular anti-tumor necrosis factor α (anti-TNFα) agents. Uveitis is known to be the most frequent extra-articular feature in HLA-B27-associated spondyloarthritides. Topical corticosteroids and cycloplegic agents remain the cornerstones of treatment. However, biologic therapy may be effective in the management of refractory or recurrent forms of uveitis. This review gives an update on the management of HLA-B27-associated ocular disorders with biologics, including anti-TNFα agents and non-anti-TNFα biologic modifier drugs. There is an emerging role for newer biologics targeting interleukin-12/23 and interleukin-17 for the treatment of spondyloarthritides but data on their efficacy on anterior uveitis are sparse.     

Association between lumican gene -1554 T/C polymorphism and high myopia in Asian population:a meta-analysis

Uveitis is one of the most important causes of blindness worldwide. Its etiology and pathogenesis are complicated and have not been well understood. The treatment for uveitis is predominantly based on steroids and immunosuppressants. However, systemic side effects limit their clinical application. With the advancement of molecular biology, some intravitreal implants and biologic agents have been used for the treatment of uveitis. Additionally, novel techniques such as gene therapy and RNA interference are being studied for using as uveitis therapy. This paper reviews recent advances in uveitis treatment.     

New options for uveitis treatment

Simulation can be defined as malingering, or sometimes functional visual loss (FVL). It manifests as either simulating an ophthalmic disease (positive simulation), or denial of ophthalmic disease (negative simulation). Conscious behavior and compensation or indemnity claims are prominent features of simulation. Since some authors suggest that this is a manifestation of underlying psychopathology, even conversion is included in this context. In today’s world, every ophthalmologist can face with simulation of ophthalmic disease or disorder. In case of simulation suspect, the physician’s responsibility is to prove the simulation considering the disease/disorder first, and simulation as an exclusion. In simulation examinations, the physician should be firm and smart to select appropriate test(s) to convince not only the subject, but also the judge in case of indemnity or compensation trials. Almost all ophthalmic sensory and motor functions including visual acuity, visual field, color vision and night vision can be the subject of simulation. Examiner must be skillful in selecting the most appropriate test. Apart from those in the literature, we included all kinds of simulation in ophthalmology. In addition, simulation examination techniques, such as, use of optical coherence tomography, frequency doubling perimetry (FDP), and modified polarization tests were also included. In this review, we made a thorough literature search, and added our experiences to give the readers up-to-date information on malingering or simulation in ophthalmology.     

Biologic agents in experimental autoimmune uveitis

Experimental uveitis models were developed in an effort to elucidate the pathogenesis of human uveitis. The therapeutic effects of numerous anti-inflammatory agents including corticosteroids and immunomodulatory agents including biologic response modifiers have been investigated in both experimental and human uveitis. Monoclonal antibodies to tumor necrosis factor alpha and anti-interleukins, among others, demonstrate efficacy and are employed in the treatment of uveitis refractory to conventional immunomodulatory agents.     

Anti-TNF-Therapie bei Uveitis

Biologicals are selectively acting proteins that demonstrated high efficacy in the treatment of chronic disorders. In particular, biologicals blocking tumor necrosis factor α (TNF-α), an essential cytokine in chronic inflammatory diseases, have demonstrated great promise. Experimental and clinical data indicate that TNF-α plays an important role in intraocular inflammation. Neutralization of TNF-α might therefore be a promising strategy for prevention and treatment of uveitis. Here we review the principle effects, therapeutic value, and potential side effects of anti-TNF agents in uveitis.     

葡萄膜炎的研究进展

葡萄膜炎是发生于眼内组织的炎性反应,是一种世界范围内的常见致盲眼病之一。其病因和临床类型近年来已发生了一些变化,发病机制的研究取得了较大进展,一些新的诊断技术、免疫抑制剂及生物制剂的应用已提高了葡萄膜炎的治疗效果。     

Biologics in the treatment of uveitis

PURPOSE OF REVIEW: This review summarizes the current evidence for biologic therapies in the treatment of uveitis. The review emphasizes published research in this field since 2005. RECENT FINDINGS: The anti-tumour necrosis factor-alpha infliximab and adalimumab have demonstrated significant efficacy in controlling uveitis associated with seronegative spondyloarthropathies and juvenile idiopathic arthritis; however, etanercept has failed to show a similar treatment effect in uveitis associated with these conditions. The majority of reports of biologic therapies in posterior uveitis have been uncontrolled trials, or retrospective studies, of uveitis resistant to immunosuppression. Encouragingly, successful control of such refractory intraocular inflammation has been consistently reported with infliximab and interferon alpha, particularly Behcet's disease-associated uveitis. A limited number of reports of anti-interleukin therapies, daclizumab and anakinra, have supported a role for these therapies in some types of uveitis. SUMMARY: Biologic therapies have increased the treatment options for sight-threatening uveitis. Despite experimental rationale, the lack of evidence from randomized controlled studies limits our understanding of when to commence therapy, which agent to choose and how long to continue treatment. Additionally, the high cost and potential side effects of all biologic agents have limited their current use to uveitis refractory to immunosuppression.     

Nonsteroidal drugs for the treatment of noninfectious posterior and intermediate uveitis

PURPOSE OF REVIEW: This review summarizes current nonsteroidal drug therapies for noninfectious posterior and intermediate uveitis. RECENT FINDINGS: Continuing evidence shows that second-line agents including antimetabolites, T-cell inhibitors and alkylating agents, are effective in many patients, allowing reduction in steroid dose and preservation of visual function. There is an increased use of mycophenolate mofetil. Biologic therapies, including the antitumour necrosis factor-alpha agents and interferons, have demonstrated a high degree of efficacy in controlling uveitis refractory to immunosuppressants. SUMMARY: There are an increasing number of treatment options. As the vast majority of published studies in uveitis are case series or nonrandomized trials, there remains a lack of level 1 evidence to guide the choice and duration of therapy. Standard initial treatment for steroid-resistant disease is to add a single immunosuppressant to the regime, with additional agents being substituted or added as required. Combination of two immunosuppressants in addition to steroids may be indicated especially in chronic uveitis. High cost and limited long-term experience with biologic agents have restricted their use to uveitis refractory to immunosuppressants, but evidence suggests a potential therapeutic role earlier in Bechet's disease.     

What is new HLA-B27 acute anterior uveitis?

Acute anterior uveitis (AAU) is the most common form of uveitis, accounting for approximately 90% of all cases. Half of all cases of AAU are HLA-B27 positive. The disease is typically acute in onset, unilateral, nongranulomatous inflammation involving the iris and ciliary body, with a tendency to recurrent attacks. Approximately 50% of all patients with HLA-B27 AAU develop an associated seronegative arthritis (SNA), while approximately 25% of the patients initially diagnosed with HLA-B27 SNA develop AAU. Environmental factors play a critical role in the pathogenesis of AAU; in particular, bacterial triggers have been strongly implicated in the development of this disease. Topical corticosteroids and cycloplegic agents remain the cornerstones of treatment for AAU. Salazopirine and methotrexate are effective in decreasing recurrent attacks. Biological agents such as anti-TNF and anti-CD20 therapy may be effective in refractory severe AU but are rarely required.