Role of cannabinoid analogs and insulin on the human cornea epithelium inflammation and cell proliferation

• Grant number: 17/09927-0
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2018
• End date: January 31, 2020
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Eduardo Melani Rocha
• Grantee: Eduardo Melani Rocha
• 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 and lacrimal secretion. However, the target mediators for possible therapeutic interventions in modulating repair are unknown. In the corneal epithelium, healing is promoted by insulin and growth factors and mediated by a good trophic and neural structure. In corneal epithelial lesions, the formation of endogenous metabolites contribute to exaggerated inflammation that delays or prevents wound closure, leads to erosion and damage to the stroma, and impairs the restoration of corneal transparency.Our general hypothesis is that cannabidiol and insulin promote balance in the inflammatory response to an aggression to the corneal epithelium. They may have secretion and paracrine action and/or lacrimal secretion.The objective of this project is to identify the effects of cannabidiol and insulin on the proliferation and inflammatory response of the corneal epithelium in culture.The techniques of corneal epithelial cell culture, treatment with cannabidiol, insulin, and challenge with LPS, capsaicin, and menthol will be followed by cytokine dosing by ELISA, qRT-PCR identification of inflammatory mediators TNF-±, MMP-2, MMP-9, IL-1² and IL-6 with or without the stimulation of agonists and antagonists of the respective receptors. Measures of proliferation, quantity and cell viability will also be made in the indicated situations. The assays will indicate the formulations to be used in animal models of corneal injury in rats exposed to 1M NaOH (single dose) or 0.2% BAC 2x day for 7 days. These conditions will be compared by direct examination, secretion tests, histology and qRT-PCR with untreated and unproven controls.The results will allow us to verify the potential dose and potentially synergistic effects of cannabidiol and insulin in therapeutic modulation strategies. The information may be useful for future application in events such as persistent epithelial defect and inflammation of the cornea. (AU)