RESUMO
Bacterial keratitis is an ocular infection that can lead to severe visual disability. Staphylococcus aureus is a major pathogen of the eye. We recently demonstrated the strong antimicrobial activity of LyeTxI-b, a synthetic peptide derived from a Lycosa erithrognatha toxin. Herein, we evaluated a topical formulation (eye drops) containing LyeTxI-b to treat resistant bacterial keratitis. Keratitis was induced with intrastromal injection of 4 × 105 cells (4 µL) in New Zealand female white rabbits. Minimum inhibitory concentration (MIC) and biofilm viability were determined. LyeTxI-b ocular toxicity was evaluated through chorioallantoic membrane and Draize tests. One drop of the formulation (LyeTxI-b 28.9 µmol/L +0.5% CMC in 0.9% NaCl) was instilled into each eye four times a day, for a week. Slit-lamp biomicroscopy analysis, corneal histopathological studies and cellular infiltrate quantification through myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) detection were performed. LyeTxI-b was very effective in the treatment of keratitis, with no signs of ocular toxicity. Planktonic bacteria MIC was 3.6 µmol/L and LyeTxI-b treatment reduced biofilm viability in 90%. LyeTxI-b eliminated bacteria and reduced inflammatory cellular activity in the eyes. Healthy and treated animals showed similar NAG and MPO levels. LyeTxI-b is a potent new drug to treat resistant bacterial keratitis, showing effective antimicrobial and anti-inflammatory activity.
Assuntos
Antibacterianos/administração & dosagem , Peptídeos Catiônicos Antimicrobianos/química , Proteínas de Artrópodes/administração & dosagem , Infecções Oculares Bacterianas/tratamento farmacológico , Ceratite/tratamento farmacológico , Soluções Oftálmicas/administração & dosagem , Venenos de Aranha/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Administração Tópica , Animais , Antibacterianos/toxicidade , Proteínas de Artrópodes/toxicidade , Galinhas , Membrana Corioalantoide/efeitos dos fármacos , Olho/efeitos dos fármacos , Olho/imunologia , Olho/patologia , Feminino , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Soluções Oftálmicas/toxicidade , Coelhos , Venenos de Aranha/toxicidade , Staphylococcus aureusRESUMO
Immunological interdependence between the two eyes has been reported for the cornea and the retina but not for the ocular mucosal surface. Intriguingly, patients frequently report ocular surface-related symptoms in the other eye after unilateral ocular surgery. Here we show how unilateral eye injuries in mice affect the mucosal immune response of the opposite ocular surface. We report that, despite the lack of lymphatic cross-drainage, a neurogenic inflammatory reflex in the contralateral conjunctiva is sufficient to increase, first, epithelial nuclear factor kappa B signaling, then, dendritic cell maturation, and finally, expansion of effector, instead of regulatory, T cells in the draining lymph node, leading to disrupted ocular mucosal tolerance. We also show that damage to ocular surface nerves is required. Using pharmacological inhibitors and agonists, we identified transient receptor potential vanilloid 1 (TRPV1) channel as the receptor sensing tissue damage in the injured eye and substance P released in the opposite ocular surface as the effector of the sympathetic response. Finally, blocking either step prevented subsequent ocular allergic reactions in the opposite eye in a unilateral corneal alkali burn model. This study demonstrates that both ocular surfaces are immunologically linked and suggests potential therapeutic targets for intervention.
Assuntos
Olho/imunologia , Inflamação/imunologia , Mucosa/imunologia , Substância P/imunologia , Canais de Cátion TRPV/imunologia , Animais , Linhagem Celular Tumoral , Células Dendríticas/imunologia , Hipersensibilidade/imunologia , Linfonodos/imunologia , Melanoma , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , NF-kappa B/imunologia , Transdução de Sinais/imunologia , Linfócitos T Reguladores/imunologiaRESUMO
Galectin-1 (Gal-1) is a ß-galactoside-binding protein with diverse biological activities in the pathogenesis of inflammation, however the mechanisms by which Gal-1 modulates cellular responses in allergic inflammatory processes have not been fully determined. In this study, we evaluated the therapeutic potential of Gal-1 eye drops in an experimental model of conjunctivitis. Wistar rats received a topical application of compound (C)48/80 (100â¯mg/ml) into right eyes and a drop of vehicle into the contralateral eye. Another group of rats received Gal-1 (0.3 or 3⯵g/eye) or sodium cromoglycate (SCG; 40â¯mg/ml) in both eyes and, after 15â¯min, right eye was challenged with C48/80. Conjunctivitis-induced by C48/80 was characterized by severe eyelid oedema and tearing, but clinical signs were ameliorated by eye drop doses of both Gal-1 (0.3/3⯵g) and SCG. As expected, an increased proportion of degranulated mast cells (62%, Pâ¯<â¯0.01) and lower histamine levels were observed after 6â¯h of C48/80 challenge, compared to control (32%). This effect was abrogated by Gal-1 and SCG, which reduced mast cell degranulation (31-36%), eosinophil migration and eosinophil peroxidase levels in the eyes. Gal-1 (3⯵g) and SCG treatments also decreased IL-4 levels, as well as activation of mitogen activated protein kinases compared to untreated C48/80 eyes. Our findings suggest that Gal-1 eye drops represent a new therapeutic strategy for ocular allergic inflammation.
Assuntos
Antialérgicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Conjuntivite Alérgica/tratamento farmacológico , Galectina 1/uso terapêutico , Animais , Antialérgicos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Degranulação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Conjuntivite Alérgica/induzido quimicamente , Conjuntivite Alérgica/imunologia , Conjuntivite Alérgica/patologia , Citocinas/imunologia , Eosinófilos/efeitos dos fármacos , Eosinófilos/enzimologia , Eosinófilos/fisiologia , Olho/efeitos dos fármacos , Olho/imunologia , Olho/patologia , Galectina 1/administração & dosagem , Histamina/imunologia , Mastócitos/efeitos dos fármacos , Mastócitos/fisiologia , Proteínas Quinases Ativadas por Mitógeno/imunologia , Soluções Oftálmicas , Peroxidases/metabolismo , Ratos Wistar , p-Metoxi-N-metilfenetilaminaRESUMO
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.
Assuntos
Oftalmopatias/imunologia , Olho/imunologia , Tolerância Imunológica , Imunidade nas Mucosas , Inflamação/imunologia , Alérgenos/imunologia , Animais , Humanos , Irritantes/imunologiaRESUMO
The progressive loss of neurons and inflammation characterizes neurodegenerative diseases. Although the etiology, progression and outcome of different neurodegenerative diseases are varied, they share chronic inflammation maintained largely by central nervous system (CNS)-derived antigens recognized by T cells. Inflammation can be beneficial by recruiting immune cells to kill pathogens or to clear cell debris resulting from the primary insult. However, chronic inflammation exacerbates and perpetuates tissue damage. An increasing number of therapies that attempt to modulate neuroinflammation have been developed. However, so far none has succeeded in decreasing the secondary damage associated with chronic inflammation. A potential strategy to modulate the immune system is related to the induction of tolerance to CNS antigens. In this line, it is our hypothesis that this could be accomplished by using anterior chamber associated immune deviation (ACAID) as a strategy. Thus, we review current knowledge regarding some neurodegenerative diseases and the associated immune response that causes inflammation. In addition, we discuss further our hypothesis of the possible usefulness of ACAID as a therapeutic strategy to ameliorate damage to the CNS.
Assuntos
Câmara Anterior/imunologia , Inflamação , Doenças Neurodegenerativas/imunologia , Doença de Alzheimer/imunologia , Esclerose Lateral Amiotrófica/imunologia , Antígenos/imunologia , Sistema Nervoso Central/imunologia , Doenças do Sistema Nervoso Central/imunologia , Olho/imunologia , Humanos , Sistema Imunitário , Tolerância Imunológica , Esclerose Múltipla/imunologia , Doenças Neurodegenerativas/terapia , Neurônios/metabolismo , Baço/imunologia , Linfócitos T Reguladores/imunologia , Timo/imunologiaRESUMO
In a cross sectional study, 19 French and 23 Colombian cases of confirmed active ocular toxoplasmosis (OT) were evaluated. The objective was to compare clinical, parasitological and immunological responses and relate them to the infecting strains. A complete ocular examination was performed in each patient. The infecting strain was characterized by genotyping when intraocular Toxoplasma DNA was detectable, as well as by peptide-specific serotyping for each patient. To characterize the immune response, we assessed Toxoplasma protein recognition patterns by intraocular antibodies and the intraocular profile of cytokines, chemokines and growth factors. Significant differences were found for size of active lesions, unilateral macular involvement, unilateral visual impairment, vitreous inflammation, synechiae, and vasculitis, with higher values observed throughout for Colombian patients. Multilocus PCR-DNA sequence genotyping was only successful in three Colombian patients revealing one type I and two atypical strains. The Colombian OT patients possessed heterogeneous atypical serotypes whereas the French were uniformly reactive to type II strain peptides. The protein patterns recognized by intraocular antibodies and the cytokine patterns were strikingly different between the two populations. Intraocular IFN-γ and IL-17 expression was lower, while higher levels of IL-13 and IL-6 were detected in aqueous humor of Colombian patients. Our results are consistent with the hypothesis that South American strains may cause more severe OT due to an inhibition of the protective effect of IFN-γ.
Assuntos
Olho/patologia , Interferon gama/análise , Interleucina-13/análise , Interleucina-17/análise , Interleucina-6/análise , Toxoplasma/isolamento & purificação , Toxoplasmose Ocular/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , DNA de Protozoário/genética , Olho/imunologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Reação em Cadeia da Polimerase , Toxoplasma/classificação , Toxoplasma/genética , Toxoplasmose Ocular/imunologia , Adulto JovemRESUMO
Vogt-Koyanagi-Harada syndrome (VKH) is a multisystem autoimmune disorder mediated by cytotoxic T cells targeting melanocytes antigen(s). A strong major histocompatibility complex (MHC) association with HLA-DRB1*04:05 has been demonstrated in different populations. We investigated the contribution of HLA-A*, -B*, -C*, -DRB1*, and -DQB1* genes, belonging to the human leukocyte antigen (HLA), to the expression of VKH and we analyzed the influence of gender on the HLA association. A total of 76 patients and 256 healthy Mexican Mestizo individuals were included. HLA-A, B, C, and DQB1 typing was performed using the polymerase chain reaction, and hybridization was done using sequence specific probes. DRB1 alleles were defined by means of sequence base typing. The frequency of DRB1*04:05 (odds ratio=2.95) and DRB1*04:04 (odds ratio=2.79) were found to be significantly increased in the patients, conferring a similar risk. Gender stratification analysis showed that these alleles were associated with female gender only. No HLA class I or class II alleles were significantly deviated in males. The frequency of DRB1*04:07 was increased in the whole group, upon withdrawal from analysis the DRB1*04:04 and *04:05 positive patients. A trend of DRB1 alleles contributing to the expression of VKH is suggested: DRB1*04:05=*04:04>*04:07>*01:01>*01:02. Although none of the results were significant after the p value was corrected, the data are consistent with those in numerous other studies, suggesting that several different DRB1* alleles may be involved in the etiopathogenesis of the disease by presenting an overlapping set of ocular peptides to the T cells, which in turn may trigger the autoimmune response that is present in the patients.
Assuntos
Olho/imunologia , Cadeias HLA-DRB1 , Síndrome Uveomeningoencefálica/imunologia , Adolescente , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Criança , Olho/patologia , Feminino , Expressão Gênica , Frequência do Gene , Antígenos HLA-A/genética , Antígenos HLA-A/imunologia , Antígenos HLA-B/genética , Antígenos HLA-B/imunologia , Antígenos HLA-C/genética , Antígenos HLA-C/imunologia , Antígenos HLA-DQ/genética , Antígenos HLA-DQ/imunologia , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/imunologia , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Fatores Sexuais , Síndrome Uveomeningoencefálica/etnologia , Síndrome Uveomeningoencefálica/genética , Síndrome Uveomeningoencefálica/patologiaRESUMO
Uveitis is a common ophthalmic disorder that can be induced in hamsters by a single intravitreal injection of bacterial lipopolysaccharide (LPS). To examine the therapeutic effects of melatonin on uveitis, a pellet of melatonin was implanted subcutaneously 2 hours before the intravitreal injection of either vehicle or LPS. Both 24 hours and 8 days after the injection, inflammatory responses were evaluated in terms of i) the integrity of the blood-ocular barrier, ii) clinical signs, iii) histopathological studies, and iv) retinal function. Melatonin reduced the leakage of proteins and cells in the anterior segment of LPS-injected eyes, decreased clinical signs such as dilation of the iris and conjunctival vessels, and flare in the anterior chamber, and protected the ultrastructure of the blood-ocular barrier. A remarkable disorganization of rod outer segment membranous disks was observed in animals injected with LPS, whereas no morphological changes in photoreceptor outer segments were observed in animals treated with melatonin. Furthermore, melatonin prevented a decrease in LPS-induced electroretinographic activity. In addition, melatonin significantly abrogated the LPS-induced increase in retinal nitric-oxide synthase activity, tumor necrosis factor-alpha, and nuclear factor kappaB p50 and p65 subunit levels. These results indicate that melatonin prevents the clinical, biochemical, histological, ultrastructural, and functional consequences of experimental uveitis, likely through a nuclear factor kappaB-dependent mechanism, and support the use of melatonin as a new therapeutic strategy for the treatment of uveitis.
Assuntos
Melatonina/uso terapêutico , Uveíte/tratamento farmacológico , Animais , Barreira Hematorretiniana/anatomia & histologia , Barreira Hematorretiniana/metabolismo , Cricetinae , Cricetulus , Modelos Animais de Doenças , Eletrorretinografia , Olho/anatomia & histologia , Olho/imunologia , Olho/patologia , Humanos , Implantes Experimentais , Lipopolissacarídeos/imunologia , Masculino , Mesocricetus , Uveíte/induzido quimicamente , Uveíte/imunologia , Uveíte/patologiaRESUMO
In the inflammosome complex, NALP3 or NALP1 binds to ASC and activates caspase-1 which induces IL-1beta. In murine LPS-induced ocular inflammation, the production of IL-1beta is increased. We suggest that NALP3- or NALP1-inflammasome complex can be participating in the LPS-induced ocular inflammation. In this work, eye, brain, testis, heart, spleen, and lung were obtained from C3H/HeN mice treated with LPS for 3 to 48 hours, and the expression of NALP1b, NALP3, ASC, caspase-1, IL-1beta, and IL-18 was determined. Infiltrated leukocytes producing IL-1beta in the anterior chamber were found at 12-hour posttreatment. A high upregulated expression of NALP3, ASC, caspase-1, IL-1beta, and IL-18 was found at the same time when infiltrated leukocytes were observed. NALP1b was not detected in the eye of treated mice. NALP3 was also overexpressed in heart and lung. These results suggest that NALP3-, but not NALP1-inflammosome complex, is participating in the murine LPS-induced ocular inflammation.
Assuntos
Proteínas de Transporte/imunologia , Olho/efeitos dos fármacos , Inflamação/induzido quimicamente , Lipopolissacarídeos/farmacologia , Animais , Antígenos/genética , Antígenos/imunologia , Proteínas de Transporte/genética , Caspase 1/metabolismo , Proteínas do Ovo/genética , Proteínas do Ovo/imunologia , Olho/imunologia , Olho/patologia , Imunidade Inata/fisiologia , Inflamação/imunologia , Interleucina-18/imunologia , Interleucina-1beta/imunologia , Interleucina-6/imunologia , Leucócitos/citologia , Leucócitos/imunologia , Lipopolissacarídeos/imunologia , Camundongos , Camundongos Endogâmicos C3H , Proteína 3 que Contém Domínio de Pirina da Família NLR , Distribuição Tecidual , Fator de Necrose Tumoral alfa/imunologiaRESUMO
The mast cell is a powerful effector cell for the innate immune system, acting through the secretion of several distinct mediators. Few studies have demonstrated the relationship between mast cells and toxoplasmosis. In this study, mast cells were investigated in two experimental Toxoplasma infections using Calomys callosus (Rodentia: Cricetidae) as the host. Animals were inoculated either intraperitoneally or via the conjunctiva with tachyzoites of Toxoplasma gondii (RH strain) and sacrificed after 5 days or 24 h, respectively. Enucleated eyes were processed for histological and ultrastructural analysis. Neither experimental infection altered the localization of mast cells compared to control eyes, but they did lead to an accumulation in some tissues as well as to their activation. There was a significant increase in the number of mast cells within 5 days and 24 h after infection. The ocular lesions were characterized by the presence of tachyzoites, inflammatory cells and vasodilatation in the iris and retina. In conclusion, mast cells were mobilized in these experimental infections, suggesting that they play an important role in the host inflammatory response after infection with T. gondii.
Assuntos
Olho/parasitologia , Mastócitos/citologia , Muridae/parasitologia , Toxoplasma/patogenicidade , Toxoplasmose Animal/imunologia , Animais , Túnica Conjuntiva/imunologia , Túnica Conjuntiva/parasitologia , Olho/citologia , Olho/imunologia , Interações Hospedeiro-Parasita , Masculino , Mastócitos/imunologia , Mastócitos/ultraestrutura , Toxoplasma/crescimento & desenvolvimento , Toxoplasmose Animal/parasitologia , Toxoplasmose Animal/patologiaRESUMO
El ojo funciona como un compartimiento aislado del resto del organismo desde el punto de vista inmunológico, lo que explica que. ante la presencia de enfermedades inflamatorias y/o infecciosas dentro del globo ocular, muchas veces no se encuentra evidencia de estas a nivel plamático. Es necesario conocer entonces las características inmunológicas normales en los fluidos intraoculares para un mejor entendimiento y manejo de las enfermedades oculares inflamatorias y/o infecciosas. En este trabajo se logró evaluar y comprobar la idemnidad de la barrera hematoocular a través de la determinación de la relación IgG/albúmina tanto en humor acuoso como en plasma cuyo coeficiente resultó ser 0,59. Además, ante la presencia de títulos positivos en sangre para toxocariasis y toxoplasmosis, no se encontró presencia de anticuerpos contra estas en los fluidos intraoculares. Finalmente los títulos de anticuerpos para lúes fueron negativos en ambos compartimentos
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Humor Aquoso/imunologia , Olho/imunologia , Uveíte/diagnóstico , Albumina Sérica , Catarata/imunologia , Glaucoma/imunologia , Imunoglobulina G , Imunoglobulina G/imunologia , Nefelometria e Turbidimetria/métodos , Toxocara/isolamento & purificação , Toxoplasma/isolamento & purificaçãoRESUMO
The present study deals with the potential role of T. gondii in inducing an arthritic inflammatory process. Wistar rats were injected subcutaneously (sc) into the right footpad with viable T. gondii trophozoites emulsified in incomplete Freund's adjuvant (IFA). The control group was injected with IFA. All parasite-injected animals developed a local inflammatory process characterized by hind limb swelling and marked restriction of ankle motility approximately 25 days after injection. Histopathogical studies of the joints, carried out 90 days after injection, revealed intense mononuclear infiltration, proliferation of granulation tissue, giant cells and necrosis in the synovia of 90% of T. gondii-injected rats. Strikingly, 40% (4/10) of the parasite-injected animals developed iridocyclitis, which was characterized by intense mononuclear infiltration around the iris-ciliary microvasculature in two animals and a slightly pronounced infiltrate of polymorphonuclear and mononuclear cells in two other animals. Antibodies to soluble T. gondii antigens (STAg) were detected in all parasite-injected rats. Antibodies against articular and ocular antigens such as proteoglycans, type II collagen, retinal S antigen and iris antigens were detected by ELISA in 40, 80, 70 and 70% of T. gondii -injected animals, respectively. Control animals injected with IFA failed to develop any articular or ocular process or humoral immune response. The present study demonstrated that footpad sc injection of Wistar rats with viable T. gondii trophozoites was able to induce a localized inflammatory arthritic process which, in some of the animals, was accompanied by iridocyclitis and immune response against articular and ocular components.
Assuntos
Artrite/imunologia , Cartilagem Articular/imunologia , Olho/imunologia , Iridociclite/imunologia , Trypanosoma/imunologia , Animais , Arrestina/imunologia , Autoantígenos , Colágeno/imunologia , Extremidades/patologia , Iris/imunologia , Articulações/patologia , Proteoglicanas/imunologia , Ratos , Ratos WistarRESUMO
Las alteraciones ultraestructurales en el glaucoma primario de ángulo abierto (GPAA) se relacionan con cambios a nivel celular y de la matriz extracelular en el tejido trabecular y pericanalicular. Los factores de crecimiento (FC) actúan como señales químicas que difunden desde las células produciendo cambios en la composición, estructura y función de la matriz extracelular. El propósito de este estudio fue describir, con la ayuda de la inmunohistoquímica, la presencia de factores de crecimiento y sus receptores en el tejido trabecular. Nuestras observaciones son sugerentes de la presencia de factor de crecimiento fibroblástico (FGF) y de su receptor (FGFr) en células trabeculares de pacientes con GPAA