Signaling of Inflammation and Cellular Proliferation of the Corneal Epithelium

• Grant number: 13/18350-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2014
• End date: August 31, 2015
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Eduardo Melani Rocha
• Grantee: Lara Cristina Dias
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Corneal diseases are among the leading causes of blindness and the mechanisms of injury and repair are largely concentrated in the epithelium, but the mediators target for possible therapeutic interventions are unknown. In the corneal epithelium, healing is impaired by activation of transient receptor potential vanilloid 1 (TRPV1). In comparing the healing of the cornea in mice without this receptor (TRPV1-/ -) and control, TRPV1-/ - is the result of much better healing. This indicates that the lesions of the corneal epithelium formation of endogenous metabolites, activate TRPV1 channels, contributing to exaggerated inflammation which delays or prevents wound closure and preclude the restoration of corneal transparency.Our general hypothesis is that TRPV1 modulates the release of inflammatory mediators by interacting with cannabinoid receptor (CB1) receptor and tumor necrosis factor-alpha (TNF±R) through the activation of transforming growth factor activated kinase 1 (TAK1) and the interaction between these pathways promotes balance in the inflammatory response after an aggression to the corneal epithelium.To assess this, our goal is to identify the signaling mechanisms involved in the inflammatory and proliferative corneal epithelial cells.Cultivation techniques of corneal epithelial cells, measurement of cytokines by ELISA after inflammatory stimuli, and "Western blot" to identify and compare expression of TRPV1 receptors, TNF±R, CB1 and activation (phosphorylation) of TAK1 under the stimulus of agonists or antagonists the respective receivers. The results allow to identify the signaling pathways involved, the interaction between them and to propose strategies for modulating these pathways with therapeutic potential in pathological situations such as persistent epithelial defect, excessive inflammation or autoimmune processes.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

DIAS, Lara Cristina. Identification and actions of transient receptor potencial vanilloid type 1 (TRPV-1) on ocular surface and lacrimal gland. 2015. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.