title: Ocular hypertension results in retinotopic alterations in the visual cortex of adult mice.
abstract: OBJECTIVE
  Glaucoma is a group of optic neuropathies characterized by the loss of retinal ganglion cells (RGCs). Since ocular hypertension (OHT) is a main risk factor, current therapies are predominantly based on lowering eye pressure. However, a subset of treated patients continues to lose vision. More research into pathological mechanisms underlying glaucoma is therefore warranted in order to develop novel therapeutic strategies. In this study we investigated the impact of OHT from eye to brain in mice.
  
  
  METHODS
  Monocular hypertension (mOHT) was induced in CD-1 mice by laser photocoagulation (LP) of the perilimbal and episcleral veins. The impact on the retina and its main direct target area, the superficial superior colliculus (sSC), was examined via immunostainings for Brn3a, VGluT2 and GFAP. Alterations in neuronal activity in V1 and extrastriate areas V2L and V2M were assessed using in situ hybridization for the activity reporter gene zif268.
  
  
  RESULTS
  Transient mOHT resulted in diffuse and sectorial RGC degeneration. In the sSC contralateral to the OHT eye, a decrease in VGluT2 immunopositive synaptic connections was detected one week post LP, which appeared to be retinotopically linked to the sectorial RGC degeneration patterns. In parallel, hypoactivity was discerned in contralateral retinotopic projection zones in V1 and V2. Despite complete cortical reactivation 4 weeks post LP, in the sSC no evidence for recovery of RGC synapse density was found and also the concomitant inflammation was not completely resolved. Nevertheless, sSC neurons appeared healthy upon histological inspection and subsequent analysis of cell density revealed no differences between the ipsi- and contralateral sSC.
  
  
  CONCLUSIONS
  In addition to RGC death, OHT induces loss of synaptic connections and neuronal activity in the visual pathway and is accompanied by an extensive immune response. Our findings stress the importance of looking beyond the eye and including the whole visual system in glaucoma research.
authors.affiliation: a Neural Circuit Development and Regeneration Research Group, Department of Biology, KU Leuven , Leuven , Belgium .
authors.forename: Eline
authors.initials: E
authors.lastname: Dekeyster
authors.affiliation: b Laboratory of Neuroplasticity and Neuroproteomics, Department of Biology , KU Leuven , Leuven , Belgium and.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Aerts
authors.affiliation: c Department of Ophthalmology , University of Murcia and IMIB-Arrixaca , Murcia , Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Valiente-Soriano
authors.affiliation: a Neural Circuit Development and Regeneration Research Group, Department of Biology, KU Leuven , Leuven , Belgium .
authors.forename: Lies
authors.initials: L
authors.lastname: De Groef
authors.affiliation: b Laboratory of Neuroplasticity and Neuroproteomics, Department of Biology , KU Leuven , Leuven , Belgium and.
authors.forename: Samme
authors.initials: S
authors.lastname: Vreysen
authors.affiliation: a Neural Circuit Development and Regeneration Research Group, Department of Biology, KU Leuven , Leuven , Belgium .
authors.forename: Manuel
authors.initials: M
authors.lastname: Salinas-Navarro
authors.affiliation: c Department of Ophthalmology , University of Murcia and IMIB-Arrixaca , Murcia , Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Vidal-Sanz
authors.affiliation: b Laboratory of Neuroplasticity and Neuroproteomics, Department of Biology , KU Leuven , Leuven , Belgium and.
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Arckens
authors.affiliation: a Neural Circuit Development and Regeneration Research Group, Department of Biology, KU Leuven , Leuven , Belgium .
authors.forename: Lieve
authors.initials: L
authors.lastname: Moons
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D004195:Disease Models, Animal; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D017403:In Situ Hybridization; D007429:Intraocular Pressure; D008297:Male; D051379:Mice; D009798:Ocular Hypertension / Q000503:physiopathology*; D012162:Retinal Degeneration / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*; D013477:Superior Colliculi / Q000378:metabolism / Q000473:pathology*; D050819:Transcription Factor Brn-3A / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism; D014793:Visual Cortex / Q000473:pathology*; D014795:Visual Pathways / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D005904:Glial Fibrillary Acidic Protein; C494189:Pou4f1 protein, mouse; C493477:Slc17a6 protein, mouse; D050819:Transcription Factor Brn-3A; D050599:Vesicular Glutamate Transport Protein 2; C528900:glial fibrillary astrocytic protein, mouse
keywords: Glaucoma; ocular hypertension; retinal ganglion cell; superior colliculus; visual cortex