巩膜重塑和巩膜干预在眼部疾病中的研究进展

巩膜是维持眼球结构和功能的重要组织,其特有的生物力学特性能影响眼部疾病的发生和发展。巩膜生物力学特性主要由巩膜细胞外基质(ECM)决定。巩膜ECM包含不同类型胶原纤维、蛋白聚糖及其他物质。在眼部疾病中,巩膜ECM成分的含量或排布会发生变化,巩膜生物力学也相应改变,这一系列的过程可称为巩膜重塑(scleral remodeling)。近年来研究表明,在许多眼部疾病中,巩膜重塑是一个复杂且动态的过程,而许多关键信号分子及通路已被证实参与并调控这一过程。本文就目前影响眼部疾病中巩膜重塑的关键信号分子及通路进行综述,并探究巩膜干预在治疗眼部疾病中的可能性。     

Glaucome et nutrition. Rôle des facteurs nutritionnels au cours des hypertonies oculaires et du glaucome

Oxidative stress, together with uncontrolled balance of long-chain polyunsaturated fatty acids may be involved in ocular hypertonias and glaucoma. Thus, nutritional factors may play a role in the evolution of these diseases. The oxidative stress might be responsible for modifications in the trabeculum extra-cellular matrix. On one hand, apoptosis and collagen remodelling (associated with an increased intraocular pressure) are primarily influenced by hydrosoluble antioxidants such as the glutathione, and on the other hand, apoptosis reactions and elastin remodelling (correlated to the occurrence of optic atrophy) are influenced mainly by liposoluble antioxidants such as vitamin E. Besides, omega 3/ omega 6 fatty acids dietary ratio may modulate the intraocular pressure control. Omega 3 fatty acids compete with the cyclooxygenase. An omega-3-rich and omega-6-poor diet may therefore promote an increased intraocular pressure related to a defect of prostaglandin (PG) F2 synthesis and to a relative decrease in the uveoscleral drainage. To date, the real importance of such factors remains insufficiently determined, but this has been the subject of many publications. Trials are currently carried out to assess the effective involvement of these nutritional factors.     

黏蛋白MUC5AC与眼病的关系

眼表黏蛋白MUC5AC是由结膜杯状细胞分泌的大分子胶样分泌性黏蛋白,其溶解于泪膜的水液层,具有清理眼表碎屑、防止眼表结构受到伤害、润滑眼表、促进泪液排出、维持泪膜稳定、防止病原体侵入、对眼表止血等作用.MUC5AC黏蛋白与许多眼表疾病有密切关系.感染性疾病、免疫性疾病、准分子激光手术、配戴角膜接触镜及维生素缺乏等均可引起MUC5AC表达水平的下降或反应性升高,引起多种临床症状,并使眼表抵御外界侵袭的能力下降,发生干眼、眼表过敏性疾病、变性类疾病等.     

Vitamin metabolism and therapy in ophthalmology

Vitamin deficiency states are important in the genesis of many ocular disorders. Deficiencies may be due to poor dietary intake, or to alterations in metabolism produced by some commonly prescribed medications or by certain diseases. Furthermore, some vitamins may exert important pharmacologic effects on the normal eye. The ocular effects of deficiencies and excesses of specific vitamins, and the therapeutic uses of each vitamin, are reviewed.     

人眼表微生物群与眼表疾病研究进展

眼表微生物群是人体眼表微环境的一部分,在维持其稳定中占据重要作用。许多研究对于健康与疾病状态下眼表微生物群的组成进行探究,但研究结果基于内外因素的不同而存在差异,且微生物失调与疾病之间的关系也尚未明确。近年来,随着肠道微生物与全身性疾病的研究不断深入,眼科研究者们也从中获得了一些启发,对眼表微生物群与眼表非感染性疾病的关系有了更进一步的探讨。本文将对正常眼表核心微生物群、眼部及全身性疾病眼表微生物群的变化进行综述,并讨论微生物失调引起疾病的可能机制,希望对未来眼表微生物群的进一步研究提供参考依据。     

Dupilumab-associated ocular manifestations: A review of clinical presentations and management

Dupilumab is a first-in-class biologic approved by the European Medicines Agency and the US Food and Drug Administration for the treatment of multiple atopic diseases, including atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis. Since gaining traction as an effective treatment modality, multiple reports have highlighted the many ocular side effects associated with dupilumab usage. These range from mild diseases, such as conjunctivitis, dry eyes, and blepharitis, to more severe manifestations such as intraocular inflammation and cicatrizing conjunctivitis. The pathogenesis behind these manifestations remains controversial, but are likely multi-factorial. We review the current evidence surrounding ocular manifestations of dupilumab-associated disease and proposed treatments to provide an overview of this unique disease entity. With increasing usage of dupilumab, formal recommendations regarding the treatment of dupilumab-associated ocular disease are warranted to provide standardized clinical guidance. Furthermore, it is important for health care practitioners to remain abreast with existing literature to counsel and empower patients with the knowledge surrounding contemporary treatments for atopic diseases and their associated sideeffects.     

顽固性炎性眼病与风湿病的眼部受累

炎性眼病是一种顽固性、致盲性眼病。诸多风湿性疾病如脊柱关节炎、白塞病、类风湿关节炎、干燥综合征、复发性多软骨炎、抗中性粒细胞胞浆抗体相关血管炎可以导致眼部损害,而眼的各个部位均可受到风湿病的侵犯。炎性眼病与风湿病的眼部受累有诸多相似之处。以炎性眼病为首发表现或主要表现的风湿病眼病患者易被漏诊。对于反复发作的炎性眼病患者,要关注包括风湿性疾病及感染性疾病在内的全身疾病。基于炎性眼病与风湿病眼病的诸多共同点,应提高对风湿病眼部累及的认识,加强多学科协作诊治。（眼科,2020, 29： 90-92）     

Protective role of oral antioxidant supplementation in ocular surface of diabetic patients

AIM: To investigate the effect of vitamin C and E supplementation in the levels of nitrite, nitric oxide (NO) related metabolite, and ocular surface parameters in diabetic patients. METHODS: 50 patients with non-insulin dependent diabetes mellitus were given vitamin C (1000 mg/day) and vitamin E (400 IU/day) supplementation for 10 days. Nitrite levels in tears were measured by photometric determination before and after vitamin supplementation. Tear function parameters (Schirmer test I, BUT, ocular ferning test) and brush cytology analysis of the conjunctival epithelium were also evaluated. RESULTS: Nitrite levels were found to be significantly reduced (p<0.05) after 10 days of vitamin C and E supplementation. Improved values for Schirmer test, BUT test, and ocular ferning test were also found. Goblet cell density and grading of squamous metaplasia showed a significant improvement. CONCLUSIONS: Oxidative stress and free radical production are elevated in diabetes mellitus. Antioxidants, such as vitamin C and vitamin E, probably have an important role in reducing the oxidative damage produced by nitric oxide and other free radicals and improving the ocular surface milieu.     

Hornhautperforationen bei Vitamin-A-Mangel

PURPOSE: Vitamin A has been identified as a substantial substrate for ocular surface integrity. Vitamin A deficiency, which can be caused by different etiologies, may lead to severe complications including corneal perforation. PATIENTS: Case reports of three patients with vitamin A deficiency. The observed etiologies leading to vitamin A deficiency were: (1) primary biliary cirrhosis, (2) malnutrition induced by alcohol abuse, and (3) malabsorption syndrome caused by a graft-versus-host disease of the intestine after bone marrow transplantation. RESULTS: In all three cases vitamin A serum levels were below normal values. In two patients retinol binding protein was also reduced. Two of three had corneal perforation, which required penetrating keratoplasty (pKP). In one of these cases, pKP was performed three times on both eyes due to a rapid corneal stromal melting leading always to corneal perforation. The third case developed severe corneal thinning of both eyes with the formation of a descemetocele. Vitamin A substitution improved symptoms and ocular surface integrity. CONCLUSION: Vitamin A in combination with zinc is a crucial factor for maintaining conjunctival and corneal ocular surface integrity. Moreover, vitamin A regulates mucin production of the ocular surface epithelium, which is known to be an important part of the ocular surface defense. Several different primary diseases might cause vitamin A deficiency. Especially patients with rapid progressive corneal ulceration should be examined for vitamin A deficiency. Substitution of vitamin A should be initiated as early as possible to prevent serious disease progression.     

Metalloproteinases as mediators of inflammation and the eyes: molecular genetic underpinnings governing ocular pathophysiology

There are many vision threatening diseases of the eye affecting millions of people worldwide. In this article, we are summarizing potential role of various matrix metalloproteinases (MMPs); the Zn (2+)-dependent endoproteases in eye health along with pathogenesis of prominent ocular diseases such as macular degeneration, diabetic retinopathy, and glaucoma via understanding MMPs regulation in affected patients, interactions of MMPs with their substrate molecules, and key regulatory functions of tissue inhibitor of metalloproteinases (TIMPs) towards maintaining overall homeostasis.     

自然光照对眼部的影响

自然光照由连续光谱、不同能量的光组成,光的波长越短能量越大,故其中紫外线和蓝光具有更高能量。暴露在高强度光照下可能导致眼部组织细胞损伤,进而引起各种眼部结构的病理变化。我们回顾了近年来有关光照在角结膜、晶状体、前房结构、视网膜、视神经相关疾病中的作用的研究,综述了光照在眼部可能触发的信号通路和作用机制。眼组织过度暴露在光照下会导致DNA损伤增加、蛋白质的异常修饰和聚集,以及过度的氧化应激,从而导致眼部疾病的发生发展。因此,可根据所接触的光照特性与强度,以及需要保护的眼组织类型,针对性地单独或联合使用物理保护、局部和/或口服抗氧化剂和光照活化信号通路的小分子抑制剂,以防止和减少光照引起的眼部损害。     

Effects of sunlight on the eye

Sunlight consists of lights of continuous spectra. Ultraviolet light and blue light in the sunlight have higher energy. High dose exposure to sunlight can cause direct cellular damage. In the eye, sunlight is known to cause pathological changes in various eye structures. We reviewed the studies on the role of sunlight in corneal diseases, cataracts, glaucoma, and age-related macular degeneration in recent years. Possible sunlight-triggered signaling pathways and mechanisms in the eye are summarized. Excessive exposure to sunlight may lead to increased DNA damage, aberrant protein modification and aggregation, and oxidative stress of ocular tissues, and thus results in the development of ocular diseases. Accordingly, physical protection, topical and/or oral antioxidants and small molecules blocking sunlight-activated signal pathways could be used independently or combinedly to prevent and reduce sunlight-induced ocular damages.     

翼状胬肉发病机制的研究进展

翼状胬肉是局部球结膜纤维血管组织增生侵犯角膜的一种疾病,是人类常见的眼表疾病之一,该病不仅直接影响面部美观,还可能由于牵拉引起眼部不适和散光,严重者影响视力且引起眼球运动障碍。关于该病的发病机制尚不明确,临床治疗以手术切除为主,但术后复发率较高。许多科学家对其发病机制提出了多种解释,创立了多种学说,但尚未有一种得到公认。明确认识翼状胬肉的发病机制,对于阻止翼状胬肉的发生、发展的研究具有重大的战略和现实意义。现就国内外在细胞凋亡抑制、基质金属蛋白酶、氧化应激、免疫方面的研究进行综述。     

Neovascularisation: Has the angiogenic factor already been found?

Recently many soluble growth factors capable of influencing neovascularisation (angiogenesis) have been isolated and molecularly cloned. As such they are now available in a highly purified and active form. One or several of these already quite well known molecules may be of importance in the control of ocular neovascularisation. This article reviews what is presently known about growth factor control of neovascularisation with particular emphasis on both the eye and those factors that have already been molecularly cloned. In addition several recently reported inhibitors of neovascularisation are discussed. Such research is of particular interest to the ophthalmologist as knowledge gained in this area may allow for the use of both growth factors as well as growth factor inhibitors in the management of several ocular diseases involving neovascularisation.     

Obesity and eye diseases

The prevalence of obesity has reached epidemic proportions in many countries. Although its impact on overall health is well documented, less is known about the ocular manifestations of obesity. Among different eye diseases, obesity has been linked with age-related cataract, glaucoma, age-related maculopathy, and diabetic retinopathy. Numerous population-based and prospective studies support an association between obesity and risk of age-related cataract. However, the nature and strength of these associations, particularly with the different cataract subtypes, remains to be determined. There is strong evidence that obesity is associated with elevated intraocular pressure, but there is no convincing data to support a more direct association between obesity and glaucomatous optic neuropathy. Studies to date have not found a consistent pattern of association between obesity and risk of age-related maculopathy or diabetic retinopathy. Thus, although obesity may be a risk factor for many ocular conditions, the present literature is inadequate to establish any convincing associations. Furthermore, whether weight loss reduces the risk of eye diseases remains unresolved. Because of the potential public health impact of obesity, there is a greater need to understand its ocular effects.     

Neovascularisation: has the angiogenic factor already been found?

Recently many soluble growth factors capable of influencing neovascularisation (angiogenesis) have been isolated and molecularly cloned. As such they are now available in a highly purified and active form. One or several of these already quite well known molecules may be of importance in the control of ocular neovascularisation. This article reviews what is presently known about growth factor control of neovascularisation with particular emphasis on both the eye and those factors that have already been molecularly cloned. In addition several recently reported inhibitors of neovascularisation are discussed. Such research is of particular interest to the ophthalmologist as knowledge gained in this area may allow for the use of both growth factors as well as growth factor inhibitors in the management of several ocular diseases involving neovascularisation.     

基质金属蛋白酶及其抑制剂在眼表疾病发病机制研究中的进展

基质金属蛋白酶(matrix metalloproteinases,MMPs)是一组降解细胞外基质的内源性蛋白酶系,其与基质金属蛋白酶组织抑制剂(tissue inhibitor of metalloproteinases,TIMPs)组成MMPs/TIMPs系统,降解和重塑细胞外基质.MMPs/TIMPs系统表达水平的失衡与眼病的发生发展密切关联,尤其是在各类眼表疾病中.目前认为结膜成纤维细胞中MMP-1、MMP-3及MMP-9过度表达是引起MMPs与TIMPs之间失去平衡的关键因素.MMPs与TIMPs之间失去平衡,使胶原纤维融解,弹力纤维变性减少,导致球结膜基质和Tenon囊的过度降解,引起眼表泪液异常的病理循环.眼表泪液的异常破坏了眼表环境的稳定性,参与多个眼表疾病如干眼、结膜松弛症、翼状胬肉、角膜炎等的病理变化.     

Ocular diseases: immunological and molecular mechanisms

Many factors, such as environmental, microbial and endogenous stress, antigen localization, can trigger the immunological events that affect the ending of the diverse spectrum of ocular disorders. Significant advances in understanding of immunological and molecular mechanisms have been researched to improve the diagnosis and therapy for patients with ocular inflammatory diseases. Some kinds of ocular diseases are inadequately responsive to current medications; therefore, immunotherapy may be a potential choice as an alternative or adjunctive treatment, even in the prophylactic setting. This article first provides an overview of the immunological and molecular mechanisms concerning several typical and common ocular diseases; second, the functions of immunological roles in some of systemic autoimmunity will be discussed; third, we will provide a summary of the mechanisms that dictate immune cell trafficking to ocular local microenvironment in response to inflammation.     

Applications of nanoparticles in ophthalmology

Nanocarriers, such as nanoparticles, have the capacity to deliver ocular drugs to specific target sites and hold promise to revolutionize the therapy of many eye diseases. Results to date strongly suggest that ocular medicine will benefit enormously from the use of this nanometric scale technology. One of the most important handicaps of the eye as a target organ for drugs is the presence of several barriers that impede direct and systemic drug access to the specific site of action. Superficial barriers include the ocular surface epithelium and the tear film, and internal barriers include the blood–aqueous and blood–retina barriers. Topical application is the preferred route for most drugs, even when the target tissues are at the back part of the eye where intraocular injections are currently the most common route of administration. Direct administration using any of these two routes faces many problems related to drug bioavailability, including side effects and repeated uncomfortable treatments to achieve therapeutic drug levels. In this regard, the advantages of using nanoparticles include improved topical passage of large, poorly water-soluble molecules such as glucocorticoid drugs or cyclosporine for immune-related, vision-threatening diseases. Other large and unstable molecules, such as nucleic acids, delivered using nanoparticles offer promising results for gene transfer therapy in severe retinal diseases. Also, nanoparticle-mediated drug delivery increases the contact time of the administered drug with its target tissue, such as in the case of brimonidine, one of the standard treatments for glaucoma, or corticosteroids used to treat autoimmune uveitis, a severe intraocular inflammatory process. In addition, nanocarriers permit the non-steroidal anti-inflammatory drug indomethacin to reach inner eye structures using the transmucosal route. Finally, nanoparticles allow the possibility of targeted delivery to reach specific types of cancer, such as melanoma, leaving normal cells untouched.This review summarizes experimental results from our group and others since the beginnings of nanocarrier technology to deliver drugs to different locations in the eye. Also, it explores the future possibilities of nanoparticles not only as drug delivery systems but also as aides for diagnostic purposes.     

DNA甲基化修饰在眼科疾病发病进程中的作用研究进展

许多眼科疾病的发生发展与遗传、环境两大因素密切相关,其中表观遗传修饰是连接遗传与环境因素的重要纽带,能够通过影响基因转录或翻译影响相关基因的表达水平,在眼病的发病进程中发挥作用。DNA甲基化修饰(DNA methylation)是表观遗传修饰的重要组成部分,通常由从头甲基化、维持甲基化和去甲基化三个过程调节,在调控基因表达方面具有重要意义。目前,研究人员发现DNA甲基化修饰在角膜内皮的损伤修复、线粒体动力学调控与糖尿病视网膜病变、氧化应激反应与白内障等眼科疾病中发挥重要作用,为相关眼病的治疗提供了新的思路。本文就DNA甲基化修饰在相关眼病发展进程中的作用研究进展进行简要综述,为眼病的筛查、诊断与治疗提供新的视角与方向。