Age-related changes in ocular mucosal tolerance: Lessons learned from gut and respiratory tract immunity.

The ocular surface is the part of the visual system directly exposed to the environment, and it comprises the cornea, the first refractive tissue layer and its surrounding structures. The ocular surface has evolved to keep the cornea smooth and wet, a prerequisite for proper sight, and also protected. To this aim, the ocular surface is a bona fide mucosal niche with an immune system capable of fighting against dangerous pathogens. However, due to the potential harmful effects of uncontrolled inflammation, the ocular surface has several mechanisms to keep the immune response in check. Specifically, the ocular surface is maintained inflammation-free and functional by a particular form of peripheral tolerance known as mucosal tolerance, markedly different from the immune privilege of intraocular structures. Remarkably, conjunctival tolerance is akin to the oral and respiratory tolerance mechanisms found in the gut and airways, respectively. And also similarly, this form of immunoregulation in the eye is affected by ageing just as it is in the digestive and respiratory tracts. With ageing comes an increased prevalence of immune-based ocular surface disorders, which could be related to an age-related impairment of conjunctival tolerance. The purpose of this review was to summarize the present knowledge of ocular mucosal tolerance and how it is affected by the ageing process in the light of the current literature on mucosal immunoregulation of the gut and airways.

Drops of Lactiplantibacillus plantarum CRL 759 culture supernatant attenuates eyes inflammation induced by lipopolysaccharide.

Anti-inflammatory effect of soluble secreted compounds of probiotic bacteria was widely demonstrated as therapy for different inflammatory diseases, but was not investigated in inflammatory eye disorders. The aim of this study was to determine whether Lactiplantibacillus plantarum CRL759 cell-free supernatant reduced inflammatory parameters and clinical signs in ocular inflammations. First, we evaluated the effect of L. plantarum CRL759 supernatant in vitro on human retinal cell line, ARPE-19 cells, stimulated with lipopolysaccharide (LPS). Then, we investigated in vivo its capacity to decrease inflammation by local administration on the eyes of mice with endotoxin induced inflammation. In vitro assays demonstrated that L. plantarum CRL759 supernatant reduced the production of interleukin (IL)-6, IL-8, nitric oxide and thiobarbituric acid reactive substances in LPS-stimulated ARPE-19 cells. Our in vivo data proved that L. plantarum supernatant significantly reduced the clinical score of endotoxin treated mice and diminished levels of tumour necrosis factor alpha, interferon gamma and protein concentration in aqueous humour. Histological examination showed reduction of infiltrating inflammatory cells in the posterior segment of the eyes. As far as we know, this is the first report showing that Lactobacillus spp. supernatant administered as drops reduces some parameters of ocular inflammation. This promising strategy is safe and could alleviate symptoms and signs of ocular inflammation in people that are refractories to the conventional therapies.

Neutrophil Extracellular Traps: Current Perspectives in the Eye.

Neutrophil extracellular traps (NETs) have been the subject of research in the field of innate immunity since their first description more than a decade ago. Neutrophils are the first cells recruited at sites of inflammation, where they perform their specific functions, including the release of NETs, which consist of web-like structures composed of granule proteins bound to decondensed chromatin fibres. This process has aroused interest, as it contributes to understanding how pathogenic microorganisms are contained, but they are also associated with pathophysiological processes of a wide range of diseases. Currently, there are growing reports of new molecules involved in the formation and release of NETs. However, whether the release of NETs contributes to eye diseases remains unclear. For this reason, the overall aim of this review is to gather current data of recent research in the ophthalmology field, where there is still much to discover.

Mucosal immune tolerance at the ocular surface in health and disease.

The ocular surface is constantly exposed to environmental irritants, allergens and pathogens, against which it can mount a prompt immune response to preserve its integrity. But to avoid unnecessary inflammation, the ocular surface's mucosal immune system must also discriminate between harmless and potentially dangerous antigens, a seemingly complicated task. Despite its unique features, the ocular surface is a mucosal lining, and as such, it shares some homeostatic and pathophysiological mechanisms with other mucosal surfaces. The purpose of this review is to explore the mucosal homeostatic immune function of the ocular surface in both the healthy and diseased states, with a special focus on mucosal immunology concepts. The information discussed in this review has been retrieved by PubMed searches for literature published from January 1981 to October 2016.

Alergia ocular / Ocular allergy

En el presente artículo revisaremos los aspectos más relevantes de la alergia ocular: su epidemiología, fisiopatología, cuadros clínicos y su terapéutica. Se encontrará una descripción más detallada de la fisiopatología ya que es, sin duda, la base del éxito terapéutico

In the present article we will review the most important aspectsof ocular allergy: its epidemiology, physiopathology, clinicalcharacteristics and treatment. A more detailed description ofthe physiopathology is addressed because is the basis for asuccessful treatment.

Human eyelid meibomian glands and tarsal muscle are recognized by autoantibodies from patients affected by a new variant of endemic pemphigus foliaceus in El-Bagre, Colombia, South America.

BACKGROUND: Previously, we described a new variant of endemic pemphigus foliaceus (EPF) in Colombia, South America (El Bagre-EPF). OBJECTIVE: Continuing our characterization of this variant of EPF, we now focus on one of our previously reported clinical findings: the presence of ocular lesions. These ocular lesions are seen in patients having extensive skin involvement, as measured by the Lund and Browder scale, which is generally used for patients with skin burns. METHODS: We specifically searched for evidence of autoreactivity to various eyelid structures in these patients and correlated our immunologic data with the clinical findings. We performed indirect immunofluorescence studies using normal-appearing human eyelid skin from routine blepharoplasties as substrate tissue. We tested sera from 12 patients with El Bagre-EPF and ocular lesions, 5 patients with sporadic (nonendemic) pemphigus foliaceus, and 20 healthy control subjects (10 from the El Bagre-EPF endemic area and 10 from nonendemic areas). We used fluorescein isothiocyanate conjugated goat antiserum to human total IgG/IgA/IgM as a secondary antibody. In addition, we used fluorescein isothiocyanate conjugated antibodies to human fibrinogen, albumin, IgG, IgE, C1q, and C3, Texas Red (Rockland Immunochemicals, Inc, Gilbertsville, PA), Alexa Fluor 555, or Alexa Fluor 594 (Invitrogen, Carlsbad, CA). Ki-67 (a cell proliferation marker) was used to determine the cell proliferation rate, and nuclear counterstaining was performed with either 4', 6-diamidino-2-phenylindole or Topro III (Invitrogen, Carlsbad, CA). RESULTS: We observed autoreactivity to multiple eyelid structures, including meibomian glands and tarsal muscle bundles at different levels, and some areas of the epidermis and the dermis close to the isthmus of the eyelids. Tarsal plate autoreactivity was seen in 10 of 12 of the El Bagre-EPF sera and in one control with pemphigus erythematosus. Furthermore, immunoprecipitation using an eyelid sample as a substrate with 1 mmol/L of sodium orthovanodate showed autoreactivity to several antigens, including some of possible lipid origin. LIMITATIONS: The main limitation of this study is the fact that the antigen or antigens remain unknown. CONCLUSION: We identified for the first time to our knowledge autoantibodies to meibomian glands and tarsal muscle in El Bagre-EPF. Our findings suggest that the autoantibodies to the ocular structures cause the clinical and histopathological findings in the ocular lesions in El Bagre-EPF.

A cross-sectional study of 130 Brazilian patients with Crohn's disease and ulcerative colitis: analysis of articular and ophthalmologic manifestations.

This is a cross-sectional study that analyzed the pattern and frequency of articular and ophthalmologic manifestations in patients with Crohn's disease (CD) and ulcerative colitis (UC), with or without signs of active bowel inflammation. One hundred and thirty consecutive patients with CD (n = 71) and UC (n = 59) were examined. Simple X-rays of lumbar spine, sacroiliac joints, and calcaneal bone were performed and human leukocyte antigen (HLA)-B27 was typed. Joint manifestations occurred in 41 (31.5%) patients, 27 (38%) with CD and 14 (23.7%) with UC. Peripheral involvement occurred in 22 patients, axial involvement in five, and mixed involvement in 14. The most frequently involved joints were knees (56.1%), ankles (29.3%), and hips (29.3%), while the predominant pattern was oligoarticular (84.6%) and asymmetrical (65.6%). Enthesitis was identified in seven (5.4%) patients and inflammatory lumbar pain in 13 (10%). Eight of these patients fulfilled the diagnostic criteria for ankylosing spondylitis (6.2%). Radiographic sacroiliitis occurred in 12 patients (9.2%). Ocular abnormalities were present in six patients (6.2%), and HLA-B27 was positive in five (5.8%). In conclusion, the articular manifestations in the present study were predominantly oligoarticular and asymmetric, with a low frequency of ophthalmologic involvement and positive HLA-B27.

[Association of human histocompatibility antigens with ophthalmological disorders]. / Associação do sistema de histocompatibilidade humano com doenças oftalmológicas.

Many studies have been trying to identify genetic markers for ophthalmological diseases, including, among others, the HLA (Human Leukocyte Antigens). Localized on the short arm of chromosome 6, the human leukocyte antigen system is well known for its capacity to confer susceptibility or resistance to different diseases. In view of its accentuated polymorphism, the strength and type of association differs with the disease and sometimes, with the studied ethnic-racial group. The development of molecular methods to typify HLA alleles and recent updates of their nomenclature has contributed to a better understanding of this system. In this review, some aspects of the human leukocyte antigen system are discussed, such as the methods of detection, nomenclature and association with acute anterior uveitis, ocular cicatricial pemphigoid, young-onset keratoconus and birdshot retinochoroidopathy.

Associação do sistema de histocompatibilidade humano com doenças oftalmológicas / Association of human histocompatibility antigens with ophthalmological disorders

Vários estudos têm procurado identificar marcadores genéticos para doenças oftalmológicas. Dentre eles, destaca-se o antígeno de histocompatibilidade humano (Human Leukocyte Antigens). Situado no braço curto do cromossomo 6, o sistema antígeno de histocompatibilidade humano é conhecido por sua capacidade de conferir susceptibilidade ou proteção a diferentes doenças. Em virtude do seu acentuado polimorfismo, o tipo e a força da associação variam a depender da enfermidade e da raça (etnia) estudadas. O surgimento de métodos moleculares para tipificação dos alelos antígeno de histocompatibilidade humano e as recentes atualizações de sua nomenclatura têm contribuído para o melhor entendimento desse sistema. O presente trabalho tem por objetivos revisar a estrutura e função do sistema antígeno de histocompatibilidade humano e relatar suas associações com uveíte anterior aguda, penfigóide cicatricial ocular, ceratocone de início na juventude e retinocoroidopatia "birdshot".

The clinical performance of the Surevue, Focus, and CSI daily wear lenses in allergic and normal contact lens patients.

Sixty-three daily wear contact lens patients (42 non-allergic [66.7%] and 21 allergic [33.3%]) were randomized into three groups (CSI vs. Surevue; Focus vs. CSI; Focus vs. Surevue) and evaluated every two weeks for six months with regard to patient preferences and ranked symptom responses for 14 variables, including overall contact lens preference. Allergic patients (43.9 +/- 94.3 ng/mL) revealed significantly higher (P = .011) tear IgE levels versus non-allergic patients (15.6 +/- 25.8 ng/mL). Non-allergic patients preferred CSI over Surevue for 12 of 14 variables including overall lens preference (P < .001); CSI over Focus for 6 of 14 variables, including overall lens preference (P < .009); and Focus over Surevue for 13 of 14 variables, including overall lens preference (P < .001). In contrast, allergic patients preferred Focus over CSI for 8 of 14 variables; CSI over Surevue for 4 of 14 variables, including overall lens preference (P < .001); Focus over Surevue for 4 of 14 variables, including overall lens preference (P < .001). Surevue and Focus lenses were replaced at 4 and 8 week intervals, respectively. No significant differences in the ranked symptom responses were observed for Surevue at 4 weeks versus 2 weeks, or for Focus at 8 weeks versus 4 weeks. A regression of time versus symptom responses for non-allergic patients wearing the CSI lens revealed decreasing symptoms over time, while the allergic patients showed no significant difference.(ABSTRACT TRUNCATED AT 250 WORDS)

Variations of the prevalence of IgG and IgM antibodies to Toxocara in Trinidadian school children - abstract

Toxocara involvement in ocular lesions was suspected following the high frequency of IgG antibodies in serum samples of patients attending the Eye Clinic at the General Hospital, Port-of-Spain. Also, a high prevalence of IgG antibodies to Toxocara was found in 5-9 year-old children in certain Caribbean islands. Fifty children, aged 6-15 years with equal numbers of boys and girls, were randomly selected from 5 schools in rural South and Central Trinidad. A stool sample (examined for parasites) and a 5ml blood sample were obtained from each student. Serum from 17 patients with ocular symptoms and from 39 patients with other symptoms were also examined. Serum IgG and IgM antibodies (to Toxocara) were determined by ELISA method. Fifty children from one school were given a thorough eye examination. The prevalence of antibodies seemed to increase with age, from 54 per cent in 5-7 year olds to 87 per cent in 12-13 year olds for IgG, and from 56 per cent to 61-63 per cent for IgM antibodies. IgG antibodies to Toxocara were more prevalent in males than females, but there was no positive correlation with reported geophagia or association with domestic pets. There was a higher prevalence of IgGs (88 per cent) in sera from patients with ocular lesions than in those without such lesions (39 per cent, p<0.01). Results suggest the need for a comprehensive study of toxocariasis in childhood in Trinidad and Tobago (AU)

Arthropathy with rash, chronic meningitis, eye lesions, and mental retardation.

Three unrelated children (one girl and two boys) have had since birth a syndrome characterized by a permanent skin rash which becomes more intense during flare-ups associated with fever, lymphadenopathy, splenomegaly, and arthritis symmetrically involving the large joints. In one boy, typical psoriasis was observed at age 3 years. In two patients, roentgenograms of the joints showed early patellar ossification and an abnormal epiphyseal appearance. The three children also had neurologic involvement, with mental retardation, enlarged head circumference, eye lesions, late closure of the anterior fontanel, and a chronic meningitis with infiltration by polymorphonuclear cells. No immunologic abnormalities were found, but polymorphonuclear cells infiltrated the skin, lymph nodes, synovial fluid, and CSF.