title: Alteration of the serine protease PRSS56 causes angle-closure glaucoma in mice and posterior microphthalmia in humans and mice.
abstract: Angle-closure glaucoma (ACG) is a subset of glaucoma affecting 16 million people. Although 4 million people are bilaterally blind from ACG, the causative molecular mechanisms of ACG remain to be defined. High intraocular pressure induces glaucoma in ACG. High intraocular pressure traditionally was suggested to result from the iris blocking or closing the angle of the eye, thereby limiting aqueous humor drainage. Eyes from individuals with ACG often have a modestly decreased axial length, shallow anterior chamber and relatively large lens, features that predispose to angle closure. Here we show that genetic alteration of a previously unidentified serine protease (PRSS56) alters axial length and causes a mouse phenotype resembling ACG. Mutations affecting this protease also cause a severe decrease of axial length in individuals with posterior microphthalmia. Together, these data suggest that alterations of this serine protease may contribute to a spectrum of human ocular conditions including reduced ocular size and ACG.
authors.affiliation: Howard Hughes Medical Institute, The Jackson Laboratory, Bar Harbor, Maine, USA.
authors.forename: K Saidas
authors.initials: KS
authors.lastname: Nair
authors.forename: Mounira
authors.initials: M
authors.lastname: Hmani-Aifa
authors.forename: Zain
authors.initials: Z
authors.lastname: Ali
authors.forename: Alison L
authors.initials: AL
authors.lastname: Kearney
authors.forename: Salma
authors.initials: S
authors.lastname: Ben Salem
authors.forename: Danilo G
authors.initials: DG
authors.lastname: Macalinao
authors.forename: Ioan M
authors.initials: IM
authors.lastname: Cosma
authors.forename: Walid
authors.initials: W
authors.lastname: Bouassida
authors.forename: Bochra
authors.initials: B
authors.lastname: Hakim
authors.forename: Zeineb
authors.initials: Z
authors.lastname: Benzina
authors.forename: Ileana
authors.initials: I
authors.lastname: Soto
authors.forename: Peter
authors.initials: P
authors.lastname: Söderkvist
authors.forename: Gareth R
authors.initials: GR
authors.lastname: Howell
authors.forename: Richard S
authors.initials: RS
authors.lastname: Smith
authors.forename: Hammadi
authors.initials: H
authors.lastname: Ayadi
authors.forename: Simon W M
authors.initials: SW
authors.lastname: John
mesh_terms: D000818:Animals; D000867:Anterior Chamber / Q000002:abnormalities; D004195:Disease Models, Animal; D005124:Eye Abnormalities / Q000235:genetics; D008040:Genetic Linkage; D015812:Glaucoma, Angle-Closure / Q000235:genetics*; D006801:Humans; D007908:Lens, Crystalline / Q000002:abnormalities; D051379:Mice; D008850:Microphthalmos / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D012160:Retina / Q000378:metabolism; D057057:Serine Proteases / Q000235:genetics* / Q000378:metabolism
chemical_list: C558176:PRSS56 protein, human; D057057:Serine Proteases