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| Author(s): |
Lara Cristina Dias
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2015-11-13 |
| Examining board members: |
Eduardo Melani Rocha;
Rubens Bertazolli Filho;
Maria de Lourdes Veronese Rodrigues
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| Advisor: | Eduardo Melani Rocha |
| Abstract | |
Corneal diseases are among the leading causes of blindness.Damage and repair mechanisms are largely concentrated in the epithelium, but the mediators and targets for possible therapeutic interventions are poorly understood. The aggressions to the corneal epithelium, the activation of vanilloid receptors transient potential 1 (TRPV1) leads to inflammatory and wound healing. The aim of this study is to identify the signaling mechanisms and TRPV1 response in the cornea of experimental animals.The culture of epithelial cells from rat cornea, to identify mediators by western blot analysis, measurement of calcium influx, cytokine response measured by PCR real time (mRNA) and ELISA (protein) nocioceptivos or after inflammatory stimuli; and the histological and immunohistochemical investigation in animal models are mice with diabetes mellitus (DM) for 8 weeks, and exposed to benzalkonium chloride at 0.2% (BAC) for 7 days. Mice TRPV1-/- compared to control C57 were compared with no stimulus, or under single stimulation with 1 µM Capsaicine (CAP), BAC 0.2% for 7 days or after the alkali burn with NaOH 1 M.The results showed the presence of TRPV1 in corneal epithelium in primary culture, showed that these cells respond to calcium influx the stimulus with capsaicin agonist 1?M and increase of TNF? and IL-1? (being maximum at the CAP + CPZ combinations and Win + CAP, respectively). In rats with DM and BAC occurs reducing the expression of IL-1? mRNA (p = 0.0269) in the cornea, among other changes. The TRPV1-/- mice have physical phenotype and normal ocular but low sensitivity to CAP 1?M. Treatment with BAC leads to decreased tear secretion (p = 0.0011) and IL-1? and TNF? in the lacrimal gland (GL) of TRPV1-/- mice (p = 0.0177, p = 0.0245, respectively) . The alkaline burn with NaOH 1M resulted in better healing and greater epithelial thickness in TRPV1-/- group .In conclusion, TRPV1 is present in the cornea and operates in response to external aggressions. Situations existing as DM and xi toxicity BAC recognized as neuropathic decrease the expression of inflammatory mediators. Genetic absence and TRPV1 does not alter the phenotype, but has lower sensitivity and better restoration of the ocular surface after alkaline burn (AU) | |
| FAPESP's process: | 13/18350-8 - Signaling of Inflammation and Cellular Proliferation of the Corneal Epithelium |
| Grantee: | Lara Cristina Dias |
| Support Opportunities: | Scholarships in Brazil - Master |