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

K. Saidas Nair, Mounira Hmani-Aifa, Zain Ali, Alison L. Kearney, Salma Ben Salem, Danilo G. MacAlinao, Ioan M. Cosma, Walid Bouassida, Bochra Hakim, Zeineb Benzina, Ileana Soto, Peter Söderkvist, Gareth R. Howell, Richard S. Smith, Hammadi Ayadi, Simon W.M. John

Research output: Contribution to journalArticle

53 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)579-584
Number of pages6
JournalNature Genetics
Volume43
Issue number6
DOIs
StatePublished - Jun 2011

All Science Journal Classification (ASJC) codes

  • Genetics

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    Nair, K. S., Hmani-Aifa, M., Ali, Z., Kearney, A. L., Salem, S. B., MacAlinao, D. G., Cosma, I. M., Bouassida, W., Hakim, B., Benzina, Z., Soto, I., Söderkvist, P., Howell, G. R., Smith, R. S., Ayadi, H., & John, S. W. M. (2011). Alteration of the serine protease PRSS56 causes angle-closure glaucoma in mice and posterior microphthalmia in humans and mice. Nature Genetics, 43(6), 579-584. https://doi.org/10.1038/ng.813