Involvement of the annexin A1-Fpr anti-inflammatory system in the ocular allergy.

Annexin A1 (ANXA1)-formyl peptide receptor (Fpr) system is potent effective mediators in the control of the inflammatory response. In this study, we evaluate the potential involvement of the Fpr family in the protective effect of the mimetic peptide of ANXA1 (ANXA12-26) using an experimental allergic conjunctivitis (AC) model in mice. Ovalbumin (OVA)/Alum-immunized wild-type (WT) and ANXA1-null (ANXA1-/-) Balb/c mice (days 0 and 7) were challenged by eye drops containing OVA on days 14-16, and two groups received ANXA12-26 alone or with Fpr antagonist Boc2 intraperitoneally during challenged days. As expected, plasma IgE anti-OVA levels increased significantly in the OVA-immunized WT and ANXA1-/- mice, supporting the efficacy of AC model. AC increased Fpr1 and Fpr2 levels in the conjunctiva and the lack of endogenous ANXA1 exacerbated Fpr2 expression only. In contrast, administering ANXA12-26 in the WT mice diminished Fpr2 levels in the conjunctiva, and the effect was reverted by Boc2. Ultrastructural analysis showed the co-localization of Fpr2 and ANXA1 in the plasma membrane of mast cells (MCs), eosinophils and neutrophils, supporting this system as being operative in the AC. Boc2 abrogated the ANXA12-26 effect by increasing the MC degranulation and the eosinophil influx in the conjunctiva, and these findings were supported by peroxidase eosinophil, eotaxin and MC protease levels. Additionally, the ANXA12-26-Fpr system in the AC was associated with the activation of ERK and JNK. Collectively, the data provided in vivo supports the anti-allergic effects of the ANXA1-Fpr system and may serve as a therapeutic target in this ocular disorder.

Treatment with galectin-1 eye drops regulates mast cell degranulation and attenuates the severity of conjunctivitis.

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 (100 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 µg/eye) or sodium cromoglycate (SCG; 40 mg/ml) in both eyes and, after 15 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 µg) and SCG. As expected, an increased proportion of degranulated mast cells (62%, P < 0.01) and lower histamine levels were observed after 6 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 µg) 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.

Tacrolimus eye drops as monotherapy for vernal keratoconjunctivitis: a randomized controlled trial.

PURPOSE: To assess the efficacy of monotherapy using tacrolimus eye drops versus sodium cromoglycate for the treatment of vernal keratoconjunctivitis (VKC). METHODS: Randomized double-masked controlled trial comparing the efficacy of tacrolimus 0.03% eye drops t.i.d. (Group 1) with sodium cromoglycate 4% eye drops t.i.d. (Group 2) for the symptomatic control of VKC at days 0, 15, 30, 45, and 90 of follow-up. Visual acuity, intraocular pressure, and other complications were evaluated to assess safety and side effects. RESULTS: In total, 16 patients were included, with 8 enrolled in each group. Two patients from Group 2 were excluded from the analysis at days 45 and 90 because of corticosteroid use. Most patients were male (81.8%) and presented with limbal VKC (56.3%). There were statistically significant differences in favor of tacrolimus in the following severity scores: itching at day 90 (p=0.001); foreign body sensation at day 15 (p=0.042); photophobia at day 30 (p=0.041); keratitis at day 30 (p=0.048); and limbal activity at days 15 (p=0.011), 30 (p=0.007), and 45 (p=0.015). No relevant adverse effects were reported, except for a burning sensation with tacrolimus, though this did not compromise treatment compliance. CONCLUSION: Treatment with tacrolimus was superior to sodium cromoglycate when comparing severity scores for symptoms of itching, foreign body sensation, and photophobia, as well as for signs of limbal inflammatory activity and keratitis.

Tacrolimus eye drops as monotherapy for vernal keratoconjunctivitis: a randomized controlled trial / Colírio de Tacrolimus 0, 03% como único agente antialérgico para o tratamento de ceratoconjuntivite primaveril: ensaio clínico randomizado

ABSTRACT Purpose: To assess the efficacy of monotherapy using tacrolimus eye drops versus sodium cromoglycate for the treatment of vernal keratoconjunctivitis (VKC). Methods: Randomized double-masked controlled trial comparing the efficacy of tacrolimus 0.03% eye drops t.i.d. (Group 1) with sodium cromoglycate 4% eye drops t.i.d. (Group 2) for the symptomatic control of VKC at days 0, 15, 30, 45, and 90 of follow-up. Visual acuity, intraocular pressure, and other complications were evaluated to assess safety and side effects. Results: In total, 16 patients were included, with 8 enrolled in each group. Two patients from Group 2 were excluded from the analysis at days 45 and 90 because of corticosteroid use. Most patients were male (81.8%) and presented with limbal VKC (56.3%). There were statistically significant differences in favor of tacrolimus in the following severity scores: itching at day 90 (p=0.001); foreign body sensation at day 15 (p=0.042); photophobia at day 30 (p=0.041); keratitis at day 30 (p=0.048); and limbal activity at days 15 (p=0.011), 30 (p=0.007), and 45 (p=0.015). No relevant adverse effects were reported, except for a burning sensation with tacrolimus, though this did not compromise treatment compliance. Conclusion: Treatment with tacrolimus was superior to sodium cromoglycate when comparing severity scores for symptoms of itching, foreign body sensation, and photophobia, as well as for signs of limbal inflammatory activity and keratitis.

RESUMO Objetivo: Demonstrar a eficácia do colírio de tacrolimus 0,03% como único agente antialérgico versus o colírio de cromoglicato de sódio 4% no tratamento de ceratoconjuntivite primaveril (CCP). Métodos: Ensaio clínico randomizado duplo-mascarado comparando a eficácia do colírio de tacrolimus 0,03% 3 vezes ao dia, versus o colírio de cromoglicato 4% 3 vezes ao dia, no controle dos sintomas e sinais de pacientes com o diagnóstico de ceratoconjuntivite primaveril, durante o período de 3 meses, com avaliações nos dias 0, 15, 30, 45 e 90. Acuidade visual, pressão intraocular e outras possíveis complicações foram avaliadas para determinar segurança e efeitos adversos. Resultados: Dezesseis pacientes foram incluídos no estudo, sendo que oito fizeram uso de colírio de tacrolimus 0,03% (Grupo 1) e oito fizeram uso de colírio de cromoglicato de sódio 4% (Grupo 2). Dois pacientes do Grupo 2 foram excluídos da análise dos dias 45 e 90, devido à necessidade de utilização de corticosteroide tópico. A maioria dos pacientes era do sexo masculino (81,8%) e 56,3% apresentavam a doença em sua forma limbar. Houve diferença estatisticamente significativa entre os Grupos 1 e 2 em relação à graduação de severidade para os sintomas de prurido no dia 90 (p=0,001), sensação de corpo estranho no dia 15 (p=0,042), fotofobia no dia 30 (p=0,041) e para os sinais de atividade inflamatória limbar nos dias 15 (p=0,011), 30 (p=0,007) e 45 (p=0,015), e ceratite no dia 30 (p=0,048). Nenhum efeito adverso relevante foi notado, exceto queixa de queimação ocular quando da instilação de tacrolimus, o que não comprometeu à adesão ao tratamento. Conclusão: O colírio de tacrolimus 0,03% foi superior ao colírio de cromoglicato de sódio 4% comparando a graduação de severidade para os sintomas de prurido, sensação de corpo estranho e fotofobia, assim como para os sinais de atividade inflamatória limbar e ceratite, em determinados períodos de tempo durante o seguimento.

Beneficial effect of annexin A1 in a model of experimental allergic conjunctivitis.

Annexin A1 (ANXA1), a 37 kDa glucocorticoid-regulated protein, is a potent anti-inflammatory mediator effective in terminating acute inflammatory response, and its role in allergic settings has been poorly studied. The aim of this investigation was to evaluate the mechanism of action of ANXA1 in intraocular inflammation using a classical model of ovalbumin (OVA)-induced allergic conjunctivitis (AC). OVA-immunised Balb/c mice, wild-type (WT) and ANXA1-deficient (AnxA1(-/-)), were challenged with eye drops containing OVA on days 14-16 with a subset of WT animals pretreated intraperitoneally with the peptide Ac2-26 (N-terminal region of ANXA1) or dexamethasone (DEX). After 24 h of the last ocular challenge, WT mice treated with Ac2-26 and DEX had significantly reduced clinical signs of conjunctivitis (chemosis, conjunctival hyperaemia, lid oedema and tearing), plasma IgE levels, leukocyte (eosinophil and neutrophil) influx and mast cell degranulation in the conjunctiva compared to WT controls. These anti-inflammatory effects of DEX were associated with high endogenous levels of ANXA1 in the ocular tissues as detected by immunohistochemistry. Additionally, Ac2-26 administration was effective to reduce IL-2, IL-4, IL-10, IL-13, eotaxin and RANTES in the eye and lymph nodes compared to untreated WT animals. The lack of ANXA1 produced an exacerbated allergic response as detected by the density of the inflammatory cell influx to the conjunctiva and the cytokine/chemokine release. These different effects observed for Ac2-26 were correlated with diminished level of activated ERK at 24 h in the ocular tissues compared to untreated OVA group. Our findings demonstrate the protective effect of ANXA1 during the inflammatory allergic response suggesting this protein as a potential target for new ocular inflammation therapies.

Síndrome de ataxia telangiectasia (enfermedad de Louis Barr): una rara facomatosis / Syndrome of ataxia telangiectasia (Louis Barr disease): a rare facomatosis

La ataxia telangiectasia o síndrome de Louis Barr es un raro desorden neurodegenerativo de carácter autosómico recesivo, caracterizado por afectación multisistémica: neurológica, oftalmológica, inmunológica, endocrina, hepática y cutánea. El complejo clínico comprende la presencia de ataxia cerebelosa progresiva, telangiectasias oculocutáneas, enfermedad sinopulmonar crónica, elevada incidencia de neoplasias y una inmunodeficiencia combinada. Es causada por mutación en el gen ataxia telangiectasia, localizado en el locus 11 q22-23, lo que da lugar a deficiencias en su expresión. Su frecuencia se calcula en 1:80.000 y 1,4 % de la población es portadora del gen. Se presenta el caso de una paciente con documentación fotográfica.

The syndrome of ataxia telangiectasia or Louis Barr disease is a rare neurodegenerative disorder autosomal recessive, characterized by multisystem involvement: neurological, immunological, endocrine, ophthalmological, hepatic and cutaneous. The clinical complex includes the presence of progressive cerebellar ataxia, ocular and cutaneous telangiectasia, chronic sinopulmonar disease, high incidence of neoplasms and combined immunodeficiency. It is caused by mutation in the gene for ataxia telangiectasia, located in the q22-23 11 locus, which leads in its expression to numerous deficiencies. Its frequency is calculated in 1:80.000, and 1,4% of the population is a carrier of the gene. The case of a patient with photographic documentation is presented.

Conjuntivitis Alérgica Resultados del tratamiento en niños / Allergic conjunctivitis Results in the treatment of children

Con el objetivo de valorar los resultados del manejo y tratamiento de los niños con conjuntivitis alérgica, se realizó un estudio descriptivo de corte transversal en niños atendidos en el Hospital General Docente Guillermo Domínguez López del municipio Puerto Padre, en el período de enero 2009 hasta enero 2010. La muestra estuvo constituida por 50 niños con este diagnóstico, que acudieron a consulta especializada, evaluando diferentes variables tales como: edad, sexo, tiempo de evolución de la enfermedad, lesiones oculares presentes, exámenes complementarios y evolución clínica. El sexo más afectado fue el masculino, con un predominio en las edades de cero a cinco años. La lesión ocular que predominó fue la infección ocular. Se comprobó que el mayor por ciento de los pacientes fueron positivos al Proteus Mirabilis, Giardia Lamblia y al polvo de la casa. Desde el punto de vista clínico predominó la evolución satisfactoria en los pacientes tratados (AU)

It is realized one descriptive study of transversal cut in 50 children attendeds with allergical conjuntivity in the General Hospital Guillermo Dominguez, in the period of January 2009-2010, its evaluate the following variables: age, sex, time evolution of the sickness, present ocular hunt, complementary examenets and clinical evaluation. The sex more affected was the masculine with one predomminant in the ages 0-5, predomming the satisfactory evaluation in the patients was try(AU)

Development of an animal model for allergic conjunctivitis: influence of genetic factors and allergen concentration on immune response.

PURPOSE: Animal models of diseases are extremely important in the study of the physiopathogenesis of human diseases and for testing novel therapeutic interventions. The present study aimed to develop an animal model that simulates human allergic conjunctivitis and to study how allergic response may be influenced by the allergen dose used for immunization and by genetic factors. METHODS: Sixty C57Bl/6 mice and 60 BALB/c mice were immunized with placebo, or 5 microg or 500 microg of allergen derived from Dermatophagoides pteronyssinus. After ocular challenge, the mice were examined in order to clinically verify the occurrence or not of conjunctivitis. Material obtained from animals was used for total and specific IgE and IgG1 dosage, for assays of Der p-specific lymphocyte proliferation and supernatant cytokine dosage, and for histopathological evaluation of conjunctiva. RESULTS: We developed a murine model of allergic conjunctivitis induced by D. pteronyssinus. The model is similar to human disease both clinically and according to laboratory findings. In mouse, conjunctivitis was associated with a Th2 cytokine profile. However, IL-10 appeared to be involved with disease blockade. Mice of different strains have distinct immune responses, depending on the sensitization dose. CONCLUSIONS: The murine model developed is suitable for the study of immunopathogenesis and as a template for future therapies. Using BALB/c and C57BL/6 mice, we demonstrated that genetic factors play a role in determining susceptibility and resistance, as well as in establishing the allergen concentration needed to induce or to block disease development.

Surgical resection of giant papillae and autologous conjunctival graft in patients with severe vernal keratoconjunctivitis and giant papillae.

PURPOSE: Giant papillae (GP) in patients with vernal keratoconjunctivitis (VKC) refractory to clinical treatment may cause serious corneal complications, such as shield ulcer. We propose a surgical treatment--resection of GP--in conjunction with free autologous conjunctival graft to treat severe cases of VKC with GP. METHODS: Six eyes of five patients with VKC, characterized by GP and shield ulcer refractory to clinical treatment, underwent surgical resection of GP associated with free autologous conjunctival graft. RESULTS: No recurrence of GP over the graft was observed during follow-up intervals ranging from 9 months to 27 months. Corneal shield ulcers healed during the first week after treatment and did not recur. CONCLUSIONS: Patients with refractory VKC and GP associated with corneal shield ulcer may benefit from resection of GP and autologous conjunctival graft.

Reactividad cutánea a alimentos en pacientes con rinoconjuntivitis alérgica / Food allergens in pacients with allergic rhinoconjunctivitis

La alergia ocular puede ser inducida por alimentos o por alergenos inhalantes; sin embargo, hay pocos estudios pediátricos al respecto. Objetivo: evaluar la relación de reactividad cutánea a alimentos y compararla con la de los inhalantes en pacientes pediátricos con rinoconjuntivitis. Método: se incluyeron 50 pacientes entre 6 y 16 años y se les realizaron pruebas a inhalantes y alimentos, IgE sérico total, citología de mucosa nasal y ocular. Para el análisis estadistico se utilizaron la prueba de T de Student no pareada, análisis de varianza de una vía, Ji cuadrada, medidas de tendencia central y dispersión. Resultados: la edad promedio fue de 9.1 años ñ 2.5 días. Las pruebas cutáneas resultaron positivas en 20 por ciento sólo para alimentos, 50 por ciento para inhalantes y 30 por ciento para ambos. Los alergenos alimentarios más frecuentes fueron mariscos, jitomate, arroz, cacahuate. El de los inhalantes fue Dermatophagoides pteronissinus. Se observó IgE sérica más elevada y citología ocular positiva en el grupo con respuesta positiva a alimentos, con diferencia significativa (p= 0.023) en relación con inhalantes. Conclusiones: en el grupo de estudio se encontraron pacientes con alergia ocular con alta frecuencia de hipersensibilidad a los alimentos (50 por ciento)

[Cutaneous reactivity to foods among patients with allergic rhinoconjunctivitis]. / Reactividad cutánea a alimentos en pacientes con rinoconjuntivitis alérgica.

Ocular allergy could be induced by food allergy or inhaled allergens. However there are few pediatric studies about it. Our objective was to know the frequency in children who have food allergy as cause of their ocular allergy. We perform a prospective and descriptive study in 50 patients within 6 to 16 years of age during June 1996 to January 1997. Skin prick tests to food allergens and inhalants, serum IgE levels by ELISA (enzyme immunoassay), nasal and conjunctival cytology were done. Not paired student T-test, Mann-Whitney U, and Kruskall-Wallis test were used for statistical analysis. We found mean of age 9.1 years +/- 2.5. Prick tests were positives to foods in 20%, 50% to inhalants and 30% to both. Food allergens seen more frequently were shellfish, tomato, rice, peanut and inhaled allergen Dermatophagoides pteronissinus. Serum IgE was elevated and ocular cytology was positive in food hypersensitivity group with significance difference (p = 0.023). In conclusion, we found a high frequency (50%) of food hypersensitivity in patients with allergic rhinoconjunctivitis.