Human Molecular Genetics Advance Access published online on October 21, 2003
Human Molecular Genetics, doi:10.1093/hmg/ddg356
© 2003 by Oxford University Press
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1 Academic Unit of Medical Genetics and Regional Genetic Service St. Mary's Hospital, Hathersage Road, Manchester, M13 OJH, UK; Academic Dept of Ophthalmology, Manchester Royal Eye Hospital, Oxford Road, Manchester, M13 9WH, UK; Centre for Molecular Medicine, Stopford Building, Oxford Road, Manchester, UK
* To whom correspondence should be addressed. E-mail: vwallace{at}ohri.ca.
Mutations in Patched (PTCH), encoding the Hh receptor, underlie Basal Cell Naevus Syndrome (BCNS) and, in addition to tumor predisposition, are associated with a wide range of ‘patterning’ defects. The basis for the underlying patterning problems in Hh-dependent tissues in BCNS and their long-term consequences on tissue homeostasis are, however, not known. Hedgehog (Hh) signaling is required for normal growth and organization of the mammalian retina and we show that PtchlacZ+/- mice exhibit vitreoretinal abnormalities resembling those found in BCNS patients. The retinas of PtchlacZ+/- mice exhibit abnormal cell cycle regulation, which culminates in photoreceptor dysplasia and Müller cell-derived gliosis. In BCNS, the intraretinal glial response results in epiretinal membrane (ERM) formation, a proliferative and contractile response on the retinal surface. Epiretinal membranes are a cause of significant visual loss in the general, especially elderly, population. We hypothesise that alteration of Müller cell Hh signaling may play a role in the pathogenesis of such age-related ‘idiopathic’ ERMs.
Article
Abnormalities of the vitreoretinal interface caused by dysregulated Hedgehog signaling during retinal development
2 Molecular Medicine Program, Ottawa Health Research Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6
3 University of Ottawa Eye Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6
4 Academic Unit of Medical Genetics and Regional Genetic Service St. Mary's Hospital, Hathersage Road, Manchester, M13 OJH, UK
5 Academic Dept of Ophthalmology, Manchester Royal Eye Hospital, Oxford Road, Manchester, M13 9WH, UK
6 Molecular Medicine Program, Ottawa Health Research Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6; University of Ottawa Eye Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6
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