UNIGE document Scientific Article
previous document  unige:22479  next document
add to browser collection

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
Lang, Karl S
show hidden authors show all authors [1 - 12]
Published in Clinical Science. 2008, vol. 114, no. 1, p. 49-58
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 alpha-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.
Keywords Acute DiseaseAnimalsBase SequenceCalcitonin Receptor-Like ProteinCiliary Body/metabolismDisease Models, AnimalEye Proteins/geneticsGlaucoma, Angle-Closure/etiology/genetics/metabolism/physiopathologyHumansIntraocular PressureIris/physiopathologyIris Diseases/complications/metabolism/physiopathologyMembrane Glycoproteins/geneticsMiceMice, TransgenicMutationOxidoreductases/geneticsReceptors, AdrenomedullinReceptors, Calcitonin/metabolism/physiologyReceptors, Peptide/metabolism
PMID: 17608625
Full text
Article (Published version) (597 Kb) - public document Free access
Research group Groupe Hafezi Farhad (ophtalmologie) (912)
(ISO format)
ITTNER, Lars M et al. Transgenic mice with ocular overexpression of an adrenomedullin receptor reflect human acute angle-closure glaucoma. In: Clinical Science, 2008, vol. 114, n° 1, p. 49-58. https://archive-ouverte.unige.ch/unige:22479

151 hits



Deposited on : 2012-08-21

Export document
Format :
Citation style :