Scientific article
Open access

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

Published inClinical science, vol. 114, no. 1, p. 49-58
Publication date2008

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.

  • Acute Disease
  • Animals
  • Base Sequence
  • Calcitonin Receptor-Like Protein
  • Ciliary Body/metabolism
  • Disease Models, Animal
  • Eye Proteins/genetics
  • Glaucoma, Angle-Closure/etiology/genetics/metabolism/physiopathology
  • Humans
  • Intraocular Pressure
  • Iris/physiopathology
  • Iris Diseases/complications/metabolism/physiopathology
  • Membrane Glycoproteins/genetics
  • Mice
  • Mice, Transgenic
  • Mutation
  • Oxidoreductases/genetics
  • Receptors, Adrenomedullin
  • Receptors, Calcitonin/metabolism/physiology
  • Receptors, Peptide/metabolism
Citation (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. doi: 10.1042/CS20070163
Main files (1)
Article (Published version)
ISSN of the journal0143-5221

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