1α,25-Dihydroxyvitamin D3 and its analog, 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD), suppress intraocular pressure in non-human primates

Ocular hypertension is the greatest known risk factor for glaucoma that affects an estimated 70 million people worldwide. Lowering intraocular pressure (IOP) remains the mainstay of therapy in the management of glaucoma. By means of microarray analysis, we have discovered that 1α,25-dihydroxyvitamin D3 (1α,25-(OH)2D3) regulates genes that are known to be involved in the determination of intraocular pressure (IOP). Topical administration of 1α,25-(OH)2D3 or its analog, 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD), markedly reduces IOP in non-human primates. The reduction in IOP is not the result of reduced aqueous humor formation, while a 35% increase in aqueous humor drainage by 1α,25-(OH)2D3 was found but this increase did not achieve significance. Nevertheless, our results suggest that 1α,25-(OH)2D3, or an analog thereof, may present a new approach to the treatment of glaucoma.

► Vitamin D modulates genes that regulate intraocular pressure. ► Topical administration of 1α,25-(OH)2D or an analog markedly reduce IOP in monkeys. ► 1α,25-(OH)2D did not change aqueous humor formation or uveoscleral outflow. ► 1α,25-(OH)2D3 or analogs provide a new approach for the treatment of glaucoma.