Improvement of Outcome Measures of Dry Eye by a Novel Integrin Antagonist in the Murine Desiccating Stress Model

Investigative Ophthalmology & Visual Science
Achim H KraussCintia S de Paiva

Abstract

We investigated the effects of GW559090, a novel, competitive, and high-affinity α4 integrin antagonist, in a murine model of dry eye. Through interaction with vascular cell adhesion molecule 1 (VCAM-1) and fibronectin α4β1 integrin is involved in leukocyte trafficking and activation. Female C57BL/6 mice, aged 6 to 8 weeks, were subjected to desiccating stress (DS). Bilateral topical twice daily treatment with GW559090 was compared to vehicle-treated controls. Treatment was initiated at the time of DS induction. Treatment effects were assessed on corneal staining with Oregon Green Dextran (OGD) and expression of inflammatory markers in ocular surface tissues by real time PCR. Dendritic cell activation was measured in draining cervical lymph nodes (CLN) by flow cytometry. Separate groups of mice received GW559090 subcutaneously to evaluate the effects of systemic administration on corneal staining and cells in CLN. Topical GW559090 significantly reduced corneal uptake of OGD compared to vehicle-treated disease controls in a dose-dependent manner (1, 3, 10, and 30 mg/mL) with 30 mg/mL showing the greatest reduction in OGD staining. When administered topically, corneal expression of IL-1α, matrix metalloproteinase (MMP)-9, chemoki...Continue Reading

Citations

Apr 5, 2016·Journal of Ophthalmology·Christopher D ConradyBhupendra C K Patel
Mar 11, 2017·International Ophthalmology Clinics·Cintia S de Paiva
Oct 17, 2017·Advanced Healthcare Materials·Michelle L RataySteven R Little
Jun 30, 2018·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Rodrigo Guimaraes de SouzaCintia S de Paiva
Nov 1, 2017·Seminars in Ophthalmology·Roberto Gonzalez-SalinasHugo Quiroz-Mercado
Jul 25, 2019·Frontiers in Chemistry·Monica BaiulaAlessandra Tolomelli
Feb 16, 2021·Frontiers in Pharmacology·Monica BaiulaSanti Spampinato
Mar 5, 2021·Experimental Eye Research·Alireza ShoariMohammad Javad Rasaee
Apr 2, 2021·Journal of Experimental Pharmacology·Monica Baiula, Santi Spampinato

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