Anti-Angiogenic and Anti-Scarring Dual Effect of Galectin-3 Inhibition in Mouse Models of Corneal Wound Healing.
Am J Pathol
; 194(3): 447-458, 2024 03.
Article
en En
| MEDLINE
| ID: mdl-38159722
ABSTRACT
Corneal scarring is the third leading cause of global blindness. Neovascularization of ocular tissues is a major predisposing factor in scar development. Although corneal transplantation is effective in restoring vision, some patients are at high risk for graft rejection due to the presence of blood vessels in the injured cornea. Current treatment options for controlling corneal scarring are limited, and outcomes are typically poor. In this study, topical application of a small-molecule inhibitor of galectin-3, GB1265, in mouse models of corneal wound healing, led to the reduction of the following in injured corneas i) corneal angiogenesis; ii) corneal fibrosis; iii) infiltration of immune cells; and iv) expression of the proinflammatory cytokine IL-1ß. Four independent techniques (RNA sequencing, NanoString, real-time quantitative RT-PCR, and Western blot analysis) determined that decreased corneal opacity in the galectin-3 inhibitor-treated corneas was associated with decreases in the numbers of genes and signaling pathways known to promote fibrosis. These findings allowed for a high level of confidence in the conclusion that galectin-3 inhibition by the small-molecule inhibitor GB1265 has dual anti-angiogenic and anti-scarring effects. Targeting galectin-3 by GB1265 is, thus, attractive for the development of innovative therapies for a myriad of ocular and nonocular diseases characterized by pathologic angiogenesis and fibrosis.
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1
Banco de datos:
MEDLINE
Asunto principal:
Cicatriz
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Lesiones de la Cornea
Límite:
Animals
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Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article