Paper from Gronert and Flanagan Labs

A new paper in the Journal of Clinical Investigation Insight for the NEI funded collaborative Glaucoma project of the Gronert and Flanagan Labs at Berkeley and Sivak Lab at the University of Toronto. Prostaglandin analogues, such as latanoprost, are the first-line treatment to reduce ocular hypertension in the management of glaucoma. The mechanism of actions for latanoprost are not well defined. The team discovered that in glaucoma patients a protective and anti-inflammatory lipid signal, lipoxin A4, was unexpectedly elevated in the aqueous humor.

Glaucoma treatment for all patients included latanoprost. Using glaucoma models, lipidomics and experiments with human trabecular meshwork cells the study revealed that latanoprost has a previously unknown dual mechanism. 1) It induced production of lipoxin A4, which inhibited pro-inflammatory signals and induced a tissue remodeling signal in the anterior chamber and 2) amplified prostaglandin production which was required for maximal latanoprost IOP lowering activity. These novel mechanisms of latanoprost are uncoupled from its established clinical IOP lowering activity and provides a foundation to investigate new hypotensive therapeutic targets with sustained anti-inflammatory and remodeling actions.