The mechanism of the antagonism of experimentally induced ocular hypertension by polyphloretin phosphate

Abstract

The ability of polyphloretin phosphate to antagonize the rise in intraocular pressure produced by prostaglandins E 2 (PGE 2), F 2α (PGF 2α) and formaldehyde has been studied in the conscious rabbit. Topical instillation of polyphloretin phosphate antagonized only the response to PGF 2α. In contrast, subconjunctival injections of polyphloretin phosphate antagonized the response of the intraocular pressure to all 3 irritants. Polyphloretin phosphate did not prevent the conjunctival vasodilation produced by all 3 irritants. Polyphloretin phosphate was separated into high and low molecular weight fractions by fractionation on Sephadex G-25 columns. Fraction I (the high molecular weight fraction) had almost no prostaglandin-blocking activity, but was a potent antagonist of hyaluronidase. Conversely Fraction III (the low molecular weight fraction) had very little anti-hyaluronidase activity, but was 2 to 5 times more potent than polyphloretin phosphate as a prostaglandin antagonist. Subconjunctival injections of Fraction I did not antagonize the response of the rabbit intraocular pressure to PGE 2 whereas Fraction III produced a significant inhibition of this response. Both Fractions I and II were found to antagonize the rise in intraocular pressure produced by formaldehyde. The present results suggest that the antiinflammatory actions of polyphloretin phosphate in the rabbit eye are due to both the prostaglandin-blocking and anti-hyaluronidase actions. It is concluded that both prostaglandin-antagonists and anti-hyaluronidase agents should be evaluated more thoroughly for use as ocular anti-inflammatory agents.