title: 1α,25-Dihydroxyvitamin D(3) and its analog, 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D(3) (2MD), suppress intraocular pressure in non-human primates.
abstract: 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 D(3) (1α,25-(OH)(2)D(3)) regulates genes that are known to be involved in the determination of intraocular pressure (IOP). Topical administration of 1α,25-(OH)(2)D(3) or its analog, 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D(3) (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)(2)D(3) was found but this increase did not achieve significance. Nevertheless, our results suggest that 1α,25-(OH)(2)D(3), or an analog thereof, may present a new approach to the treatment of glaucoma.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706-1544, United States.
authors.forename: Galina D
authors.initials: GD
authors.lastname: Kutuzova
authors.forename: B'ann T
authors.initials: BT
authors.lastname: Gabelt
authors.forename: Julie A
authors.initials: JA
authors.lastname: Kiland
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Hennes-Beann
authors.forename: Paul L
authors.initials: PL
authors.lastname: Kaufman
authors.forename: Hector F
authors.initials: HF
authors.lastname: DeLuca
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D005123:Eye / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects*; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D051381:Rats; D059467:Transcriptome / Q000187:drug effects
chemical_list: C519954:2-methylene-19-nor-(20S)-1alpha,25-dihydroxyvitamin D3; D002117:Calcitriol; D002118:Calcium