title: PAX6 Expression and Retinal Cell Death in a Transgenic Mouse Model for Acute Angle-Closure Glaucoma.
abstract: OBJECTIVE
  PAX6 is a highly conserved protein essential for the control of eye development both in invertebrates and vertebrates. PAX6 expression persists in the adult inner retina, but little is known about its functions after completion of retinal differentiation. Therefore, we investigated PAX6 expression in wild-type and calcitonin receptor-like receptor transgenic (CLR(SMαA)) mice with angle-closure glaucoma.
  
  
  METHODS
  Intraocular pressure was measured by indentation tonometry in anesthetized mice. Eyes of mice of both genotypes were enucleated at various ages and retinas were processed for morphological analysis and PAX6 immunostaining. The content of PAX6 in retinal extracts was estimated by Western blot analysis. Retinal expression of glaucoma-related genes was analyzed by reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  Control mice showed normal retinal morphology between p22 and p428 with steady PAX6 expression in the ganglion cell layer (GCL) and the inner nuclear layer (INL). CLR(SMαA) mice examined between p22 and p82 exhibited increased intraocular pressure and a progressive decrease in cell number including PAX6-expressing cells in the GCL. The INL was not affected up to postnatal day 42. Later, a significant increase in PAX6-expressing cells concomitant with an overall loss of cells was observed in the INL of CLR(SMαA) as compared with control mice. Retinal up-regulation of glaucoma-related genes was furthermore observed.
  
  
  CONCLUSIONS
  Distinctive changes of PAX6 expression in the inner retina of CLR(SMαA) mice suggest a role in regulatory mechanisms involved in glaucoma-related retinal cell death. The selective increase of PAX6 expression in the degenerating INL of CLR(SMαA) mice may represent an attempt to preserve retinal cytoarchitecture.
authors.affiliation: *Department of Ophthalmology, Charing Cross Hospital, Imperial College London, London, UK †Research Laboratory, Orthopaedic University Hospital Balgrist ‡Department of Ophthalmology, Laboratory for Retinal Cell Biology, University Hospital Zurich ∥IROC, Institute for Refractive and Ophthalmic Surgery, Zurich §University Eye Clinic Basel, Basel, Switzerland.
authors.forename: Dinu
authors.initials: D
authors.lastname: Stanescu-Segall
authors.forename: Kerstin
authors.initials: K
authors.lastname: Birke
authors.forename: Andreas
authors.initials: A
authors.lastname: Wenzel
authors.forename: Christian
authors.initials: C
authors.lastname: Grimm
authors.forename: Sorguel
authors.initials: S
authors.lastname: Orgul
authors.forename: Jan A
authors.initials: JA
authors.lastname: Fischer
authors.forename: Walter
authors.initials: W
authors.lastname: Born
authors.forename: Farhad
authors.initials: F
authors.lastname: Hafezi
mesh_terms: D000208:Acute Disease; D000818:Animals; D015153:Blotting, Western; D016923:Cell Death; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D015812:Glaucoma, Angle-Closure / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007429:Intraocular Pressure; D051379:Mice; D008822:Mice, Transgenic; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014065:Tonometry, Ocular
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins