title: Role of α₁-adrenoceptor subtypes in pupil dilation studied with gene-targeted mice.
abstract: OBJECTIVE
  The α₁A-adrenoceptor (α₁A-AR) subtype was suggested to mediate contraction and trophic effects in the iris dilator muscle, and thus its pharmacological blockade may be involved in intraoperative floppy iris syndrome. We tested the hypothesis that the α₁A-AR mediates pupil dilation and trophic effects in the mouse iris.
  
  
  METHODS
  The α₁-AR subtype mRNA expression was quantified in iris tissue by real-time PCR. To assess the role of individual α₁-ARs for mediating pupil dilation, the α₁-AR agonist phenylephrine was topically applied to the ocular surface of mice deficient in one of the three α₁-AR subtypes (α₁A-AR(-/-), α₁B-AR(-/-), α₁D-AR(-/-), respectively) and wild-type controls. Changes in pupil diameter were measured under a microscope in restrained mice. Moreover, iris and iris muscle thickness were determined in cryosections.
  
  
  RESULTS
  Messenger RNA for all three α₁-AR subtypes was detected the iris of wild-type mice with a rank order of abundance of α₁A ≥ α₁B > > α₁D. The lack of a single α₁-AR gene did not affect mRNA expression of the remaining two receptor subtypes. Phenylephrine induced pupil dilation in wild-type mice that was reduced in extent and duration in α₁A-AR(-/-) and, less so, in α₁B-AR(-/-) but not in α₁D-AR(-/-) mice. The lack of a single α₁-AR subtype had no effect on iris or iris muscle thickness.
  
  
  CONCLUSIONS
  The α₁-AR-induced mydriasis in mice is mediated mainly by the α₁A-AR, with a smaller contribution of the α₁B-AR, matching the relative abundance of these subtypes at the mRNA level. The lack of a single α₁-AR subtype does not appear to cause atrophy in the mouse iris.
authors.affiliation: Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Marcin L
authors.initials: ML
authors.lastname: Kordasz
authors.affiliation: Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Manicam
authors.affiliation: Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Steege
authors.affiliation: Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Goloborodko
authors.affiliation: Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Amato
authors.affiliation: Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Laspas
authors.affiliation: Institute of Pathology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Brochhausen
authors.affiliation: Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Pfeiffer
authors.affiliation: Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Adrian
authors.initials: A
authors.lastname: Gericke
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007498:Iris / Q000378:metabolism; D007499:Iris Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010656:Phenylephrine / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018340:Receptors, Adrenergic, alpha-1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine
keywords: IFIS; gene-targeted mice; intraoperative floppy iris syndrome; α1-adrenoceptor