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Alteration of the serine protease PRSS56 causes angle-closure glaucoma in mice and posterior microphthalmia in humans and mice

Saidas Nair, K (author)
Howard Hughes Medical Institute, The Jackson Laboratory, Maine, USA
Hmani-Aifa, Mounira (author)
Equipe Procédés de Criblages Moléculaires et Cellulaires, Laboratoire de Microorganismes et Biomolécules, Centre de Biotechnologie de Sfax, Université de Sfax, Sfax, Tunisia
Ali, Zain (author)
Howard Hughes Medical Institute, The Jackson Laboratory, Maine, USA
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Kearney, Alison L (author)
Howard Hughes Medical Institute, The Jackson Laboratory, Maine, USA
Ben Salem, Salma (author)
Equipe Procédés de Criblages Moléculaires et Cellulaires, Laboratoire de Microorganismes et Biomolécules, Centre de Biotechnologie de Sfax, Université de Sfax, Sfax, Tunisia
Macalinao, Danilo G (author)
Howard Hughes Medical Institute, The Jackson Laboratory, Maine, USA
Cosma, Ioan M (author)
Howard Hughes Medical Institute, The Jackson Laboratory, Maine, USA
Bouassida, Walid (author)
Service d’ophtalmologie, Centre Hospitalo-Universitaire Habib Bourguiba, Sfax, Tunisia.
Hakim, Bochra (author)
Equipe Procédés de Criblages Moléculaires et Cellulaires, Laboratoire de Microorganismes et Biomolécules, Centre de Biotechnologie de Sfax, Université de Sfax, Sfax, Tunisia
Benzina, Zeineb (author)
Service d’ophtalmologie, Centre Hospitalo-Universitaire Habib Bourguiba, Sfax, Tunisia.
Soto, Ileana (author)
Howard Hughes Medical Institute, The Jackson Laboratory, Maine, USA
Söderkvist, Peter (author)
Linköpings universitet,Cellbiologi,Hälsouniversitetet
Howell, Gareth R (author)
Howard Hughes Medical Institute, The Jackson Laboratory, Maine, USA
Smith, Richard S (author)
Howard Hughes Medical Institute, The Jackson Laboratory, Maine, USA
Ayadi, Hammadi (author)
Equipe Procédés de Criblages Moléculaires et Cellulaires, Laboratoire de Microorganismes et Biomolécules, Centre de Biotechnologie de Sfax, Université de Sfax, Sfax, Tunisia
John, Simon W M (author)
Howard Hughes Medical Institute, The Jackson Laboratory, Maine, USA
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 (creator_code:org_t)
2011-05-01
2011
English.
In: NATURE GENETICS. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 43:6, s. 579-U118
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  • Journal article (peer-reviewed)
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  • Angle-closure glaucoma (ACG) is a subset of glaucoma affecting 16 million people(1-3). Although 4 million people are bilaterally blind from ACG(4,5), 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(6). 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.

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