Dynasore Shows Potential as a Treatment for Ocular Surface Disease

Rose bengal and fluorescein can stain damaged conjunctival and corneal tissue in the eye. They play an important role in ophthalmology to diagnose dry eye and eye surface damage. The mechanism these stains use to stain damaged cells and not healthy ones is not understood.

Dynasore is a small molecule that inhibits dynamin. Dynamin is essential for endocytosis in eukaryotic cells, so dynasore inhibits endocytosis. Dynasore is used as a cell biology research tool.

Recently, Webster et al. proposed a mechanism for how rose bengal and fluorescein work. Sublethal cell damage causes the cell to repair itself by remodeling its plasma membrane. While remodeling the plasma membrane, the cell might take up stain via endocytosis. They tested their hypothesis by applying oxidative stress to monolayer cultures of human corneal epithelial cells. The oxidative stress caused an increase in both stain uptake and endocytosis. Then they applied the endocytosis inhibitors chlorpromazine hydrochloride, genistein, Dynasore hydrate, and Dyngo-4a (a Dynasore derivative). Stain uptake was blocked.

However, when they repeated the experiment in whole eye tissue harvested from mice, oxidative stress increased stain uptake, but did not increase endocytosis. Most of the endocytosis inhibitors did not block stain uptake. Dynasore and Dyngo-4a did.

If eye cell damage increased stain uptake but not endocytosis, endocytosis must not be the mechanism for cell uptake. Then why did two of the endocytosis inhibitors, Dynasore and its derivative, inhibit stain uptake if endocytosis was not involved?

Webster et al. performed cytotoxicity and Western blotting assays and concluded that Dynasore and Dyngo-4a prevented oxidative damage to the cells. The results have implications for the field of ophthalmology. Dynasore and Dyngo-4a may have therapeutic potential.