Transgenic mice with ocular overexpression of an adrenomedullin receptor reflect human acute angle-closure glaucoma

Ittner, Lars M., Schwerdtfeger, Kerstin, Kunz, Thomas H., Muff, Roman, Husmann, Knut, Grimm, Christian, Hafezi, Farhad, Langh, Karl S., Kurrer, Michael O., Gotz, Jurgen, Born, Walter and Fischer, Jan A. (2008) Transgenic mice with ocular overexpression of an adrenomedullin receptor reflect human acute angle-closure glaucoma. Clinical Science, 114 1-2: 49-58. doi:10.1042/CS20070163

Author Ittner, Lars M.
Schwerdtfeger, Kerstin
Kunz, Thomas H.
Muff, Roman
Husmann, Knut
Grimm, Christian
Hafezi, Farhad
Langh, Karl S.
Kurrer, Michael O.
Gotz, Jurgen
Born, Walter
Fischer, Jan A.
Title Transgenic mice with ocular overexpression of an adrenomedullin receptor reflect human acute angle-closure glaucoma
Journal name Clinical Science   Check publisher's open access policy
ISSN 0143-5221
Publication date 2008-01-01
Year available 2008
Sub-type Article (original research)
DOI 10.1042/CS20070163
Open Access Status Not Open Access
Volume 114
Issue 1-2
Start page 49
End page 58
Total pages 10
Place of publication London, United Kingdom
Publisher Portland Press Ltd.
Language eng
Subject 2700 Medicine
Abstract 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 α-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.
Keyword Adrenomedullin
Angle closure glaucoma
Calcitonin receptor like receptor (CLR)
Intraocular pressure
Pupillary palsy
Receptor-activity-modifying protein (RAMP)
Smooth muscle α actin
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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