{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T01:55:15Z","timestamp":1768010115564,"version":"3.49.0"},"reference-count":36,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,1,1]]},"abstract":"<jats:p>Glaucoma, frequently associated with high IOP (intra-ocular pressure), is a leading cause of blindness, characterized by a loss of retinal ganglion cells and the corresponding optic nerve fibres. In the present study, acutely and transiently elevated IOP, characteristic of acute angle-closure glaucoma in humans, was observed in CLR (calcitonin receptor-like receptor) transgenic mice between 1 and 3 months of age. Expression of CLR under the control of a smooth muscle \u03b1-actin promoter in these mice augmented signalling of the smooth-muscle-relaxing peptide adrenomedullin in the pupillary sphincter muscle and resulted in pupillary palsy. Elevated IOP was prevented in CLR transgenic mice when mated with hemizygote adrenomedullin-deficient mice with up to 50% lower plasma and organ adrenomedullin concentrations. This indicates that endogenous adrenomedullin of iris ciliary body origin causes pupillary palsy and angle closure in CLR transgenic mice overexpressing adrenomedullin receptors in the pupillary sphincter muscle. In human eyes, immunoreactive adrenomedullin has also been detected in the ciliary body. Furthermore, the CLR and RAMP2 (receptor-activity-modifying protein 2), constituting adrenomedullin receptor heterodimers, were identified in the human pupillary sphincter muscle. Thus, in humans, defective regulation of adrenomedullin action in the pupillary sphincter muscle, provoked in the present study in CLR transgenic mice, may cause acute and chronic atony and, thereby, contribute to the development of angle-closure glaucoma. The CLR transgenic mice used in the present study provide a model for acute angle-closure glaucoma.<\/jats:p>","DOI":"10.1042\/cs20070163","type":"journal-article","created":{"date-parts":[[2007,11,30]],"date-time":"2007-11-30T16:11:23Z","timestamp":1196439083000},"page":"49-58","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Transgenic mice with ocular overexpression of an adrenomedullin receptor reflect human acute angle-closure glaucoma"],"prefix":"10.1042","volume":"114","author":[{"given":"Lars\u00a0M.","family":"Ittner","sequence":"first","affiliation":[{"name":"Laboratory for Orthopedic Research, Orthopedic University Hospital Balgrist, University of Zurich, CH-8008 Zurich, Switzerland"},{"name":"Alzheimer's and Parkinson's Disease Laboratory, The Brain and Mind Research Institute, University of Sydney, Camperdown, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin","family":"Schwerdtfeger","sequence":"additional","affiliation":[{"name":"Laboratory for Orthopedic Research, Orthopedic University Hospital Balgrist, University of Zurich, CH-8008 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas\u00a0H.","family":"Kunz","sequence":"additional","affiliation":[{"name":"Laboratory for Orthopedic Research, Orthopedic University Hospital Balgrist, University of Zurich, CH-8008 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman","family":"Muff","sequence":"additional","affiliation":[{"name":"Laboratory for Orthopedic Research, Orthopedic University Hospital Balgrist, University of Zurich, CH-8008 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Knut","family":"Husmann","sequence":"additional","affiliation":[{"name":"Laboratory for Orthopedic Research, Orthopedic University Hospital Balgrist, University of Zurich, CH-8008 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Grimm","sequence":"additional","affiliation":[{"name":"Laboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, CH-8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farhad","family":"Hafezi","sequence":"additional","affiliation":[{"name":"Institute for Refractive and Ophthalmic Surgery, CH-8002, Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl\u00a0S.","family":"Lang","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology, University Hospital Zurich, CH-8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael\u00a0O.","family":"Kurrer","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pathology, University Hospital Zurich, CH-8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"G\u00f6tz","sequence":"additional","affiliation":[{"name":"Alzheimer's and Parkinson's Disease Laboratory, The Brain and Mind Research Institute, University of Sydney, Camperdown, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter","family":"Born","sequence":"additional","affiliation":[{"name":"Laboratory for Orthopedic Research, Orthopedic University Hospital Balgrist, University of Zurich, CH-8008 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan\u00a0A.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Laboratory for Orthopedic Research, Orthopedic University Hospital Balgrist, University of Zurich, CH-8008 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2007,11,30]]},"reference":[{"key":"2021120120531337200_B1","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1136\/bjo.80.5.389","article-title":"Number of people with glaucoma worldwide","volume":"80","author":"Quigley","year":"1996","journal-title":"Br. 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