Transglutaminase binding fusion protein linked to SLPI reduced corneal inflammation and neovascularization
Autor: | Juan Pablo Salica, Diego Guerrieri, H. Eduardo Chuluyan, Paulo Cesar Maffia, Juan E Gallo, J. O. Croxatto |
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Jazyk: | angličtina |
Předmět: |
Male
Vascular Endothelial Growth Factor A Pathology Tissue transglutaminase Administration Topical Cell Count Corneal inflammation ANGIOGENESIS Rats Sprague-Dawley Neovascularization Cementoin Re-Epithelialization Cornea Secretory Leukocyte Peptidase Inhibitor CORNEAL NEOVASCULARIZATION Fluorescent Antibody Technique Indirect Alkali injury Corneal epithelium biology Epithelium Corneal purl.org/becyt/ford/3.1 [https] General Medicine Medicina Básica Eye Burns medicine.anatomical_structure purl.org/becyt/ford/3 [https] medicine.symptom Research Article Farmacología y Farmacia medicine.medical_specialty CIENCIAS MÉDICAS Y DE LA SALUD ALKALI INJURY Recombinant Fusion Proteins NFkB GTP-Binding Proteins Burns Chemical medicine Animals Corneal Neovascularization Protein Glutamine gamma Glutamyltransferase 2 Keratitis Transglutaminases SLPI business.industry Histology medicine.disease Transglutaminase eye diseases Rats CORNEAL INFLAMMATION Disease Models Animal Ophthalmology CEMENTOIN TRANSGLUTAMINASE Corneal neovascularization biology.protein Angiogenesis sense organs business |
Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET BMC Ophthalmology |
ISSN: | 1471-2415 |
DOI: | 10.1186/1471-2415-15-12 |
Popis: | Background: To study the effect of topical administration of a fusion protein (PF-MC) made up of N-terminal portion of the protease inhibitor Trappin-2 (which is a substrate of transglutaminasa-2) and SLPI (protein with anti-inflammatory, anti-bacterial and anti-viral ability), in an animal model of corneal inflammation and angiogenesis. Methods: An alkali injury was produced with a filter paper of 3 mm with 1 N NaOH during 40 seconds on the right cornea of 36 male Sprague Dawley rats, under general anesthesia. Animals were divided into three groups according to treatment. Group 1 was treated with 10 ul of PF-MC (200 ug/ml; n = 12), Group 2, with 10 ul of SLPI (200 ug/ml; n = 12) and Group 3 was treated with buffer (10 ul; n = 12) topically administered four times a day for up to 7 days. Half of the animals were sacrificed at day 3 before making a re-epithelialization time analysis with fluorescein staining at 18 and 24 hours. In the remaining animals corneal opacity was studied and digital photographs were taken at day 7 before doing euthanasia. Eyes were processed for histology and immunofluorescence. Results: Corneal ulcerated area was significantly lower in PF-MC treated animals compared to SLPI and buffer-treated animals at 18 hours and 24 hours postinjury. A clear cornea and fundus red reflex was only found among PF-MC treated animals. Histological analysis revealed a stratified corneal epithelium with at least three layers in all PF-MC animals at day 7. In this group there was a reduced number of PMNs in the corneal stroma at 3 and 7 days of follow-up. Besides, corneal neovascularization was much more extended in SLPI and Buffer animals than in animals treated with PF-MC. Conclusions: The binding of SLPI with Cementoin to transglutaminase seems to be an effective strategy to treat corneal inflammation and angiogenesis. Fil: Salica, Juan Pablo. Universidad Austral. Facultad de Ciencias Biomedicas; Argentina. Hospital Universitario Austral. Departamento de Oftalmología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Guerrieri, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Maffia, Paulo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Croxatto, Juan Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Oftalmología Argentina "J. Malbrán"; Argentina Fil: Chuluyan, Hector Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Gallo, Juan Eduardo Maria. Universidad Austral. Facultad de Ciencias Biomedicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Universitario Austral. Departamento de Oftalmología; Argentina |
Databáze: | OpenAIRE |
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