Drug combination of topical ripasudil and brimonidine enhances neuroprotection in a mouse model of optic nerve injury

To determine whether combination of topical ripasudil and brimonidine has more effective neuroprotection on retinal ganglion cells (RGCs) following injury to axons composing the optic nerve. Topical ripasudil, brimonidine, or mixture of both drugs were administered to adult mice after optic nerve injury (ONI). The influence of drug conditions on RGC health were evaluated by the quantifications of surviving RGCs, phosphorylated p38 mitogen-activated protein kinase (phospho-p38), and expressions of trophic factors and proinflammatory mediators in the retina. Topical ripasudil and brimonidine suppressed ONI-induced RGC death respectively, and mixture of both drugs further stimulated RGC survival. Topical ripasudil and brimonidine suppressed ONI-induced phospho-p38 in the whole retina. In addition, topical ripasudil suppressed expression levels of TNFα, IL-1β and monocyte chemotactic protein-1 (MCP-1), whereas topical brimonidine increased the expression level of basic fibroblast growth factor (bFGF). Combination of topical ripasudil and brimonidine may enhance RGC protection by modulating multiple signaling pathways in the retina.