title: Detailed functional and structural characterization of a macular lesion in a rhesus macaque.
abstract: OBJECTIVE
  Animal models are powerful tools to broaden our understanding of disease mechanisms and to develop future treatment strategies. Here we present detailed structural and functional findings of a rhesus macaque suffering from a naturally occurring bilateral macular dystrophy (BMD), partial optic atrophy and corresponding reduction of central V1 signals in visual fMRI experiments when compared to data in a healthy macaque (CTRL) of similar age.
  
  
  METHODS
  Retinal imaging included infrared and autofluorescence recordings, fluorescein and indocyanine green angiography and spectral domain optical coherence tomography (OCT) on the Spectralis HRA + OCT platform. Electroretinography included multifocal and Ganzfeld-ERG recordings. Animals were killed and eyes analyzed by immunohistochemistry.
  
  
  RESULTS
  Angiography showed reduced macular vascularization with significantly larger foveal avascular zones (FAZ) in the affected animal (FAZBMD = 8.85 mm(2) vs. FAZCTRL = 0.32 mm(2)). OCT showed bilateral thinning of the macula within the FAZ (total retinal thickness, TRTBMD = 174 ± 9 µm) and partial optic nerve atrophy when compared to control (TRTCTRL = 303 ± 45 µm). Segmentation analysis revealed that inner retinal layers were primarily affected (inner retinal thickness, IRTBMD = 33 ± 9 µm vs. IRTCTRL = 143 ± 45 µm), while the outer retina essentially maintained its thickness (ORTBMD = 141 ± 7 µm vs. ORTCTRL = 160 ± 11 µm). Altered macular morphology corresponded to a preferential reduction of central signals in the multifocal electroretinography and to a specific attenuation of cone-derived responses in the Ganzfeld electroretinography, while rod function remained normal.
  
  
  CONCLUSIONS
  We provided detailed characterization of a primate macular disorder. This study aims to stimulate awareness and further investigation in primates with macular disorders eventually leading to the identification of a primate animal model and facilitating the preclinical development of therapeutic strategies.
authors.affiliation: Centre for Ophthalmology, University Eye Hospital, Schleichstr. 12-14, 72076, Tübingen, Germany. Dominik.Fischer@ndcn.ox.ac.uk|Institute for Ophthalmic Research, Centre for Ophthalmology, Schleichstr. 12-14, 72076, Tübingen, Germany. Dominik.Fischer@ndcn.ox.ac.uk.|Nuffield Laboratory of Ophthalmology, University of Oxford, Levels 5 and 6 West Wing, The John Radcliffe Hospital, Oxford, OX3 9DU, UK. Dominik.Fischer@ndcn.ox.ac.uk.
authors.forename: M
authors.initials: M
authors.lastname: Dominik Fischer
authors.affiliation: Institute for Ophthalmic Research, Centre for Ophthalmology, Schleichstr. 12-14, 72076, Tübingen, Germany.
authors.forename: Ditta
authors.initials: D
authors.lastname: Zobor
authors.affiliation: Max-Planck Institute for Biological Cybernetics, Spemannstr. 38-44, 72076, Tübingen, Germany.
authors.forename: Georgios A
authors.initials: GA
authors.lastname: Keliris
authors.affiliation: Max-Planck Institute for Biological Cybernetics, Spemannstr. 38-44, 72076, Tübingen, Germany.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Institute for Ophthalmic Research, Centre for Ophthalmology, Schleichstr. 12-14, 72076, Tübingen, Germany.
authors.forename: Mathias W
authors.initials: MW
authors.lastname: Seeliger
authors.affiliation: Neuroanatomy, Max Planck Institute for Brain Research, Deutschordenstr. 46, 60528, Frankfurt a.M., Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Haverkamp
authors.affiliation: University Eye Clinic, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Jägle
authors.affiliation: Max-Planck Institute for Biological Cybernetics, Spemannstr. 38-44, 72076, Tübingen, Germany.
authors.forename: Nikos K
authors.initials: NK
authors.lastname: Logothetis
authors.affiliation: Max-Planck Institute for Biological Cybernetics, Spemannstr. 38-44, 72076, Tübingen, Germany.|Department of Neuroscience and Neurology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
authors.forename: Stelios M
authors.initials: SM
authors.lastname: Smirnakis
mesh_terms: D000818:Animals; D004596:Electroretinography / Q000662:veterinary; D005260:Female; D005451:Fluorescein Angiography / Q000662:veterinary; D008253:Macaca mulatta; D008268:Macular Degeneration / Q000175:diagnosis / Q000503:physiopathology / Q000662:veterinary*; D008279:Magnetic Resonance Imaging / Q000662:veterinary; D008297:Male; D008992:Monkey Diseases / Q000175:diagnosis* / Q000503:physiopathology; D009896:Optic Atrophy / Q000175:diagnosis / Q000503:physiopathology / Q000662:veterinary*; D012160:Retina / Q000473:pathology*; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology; D041623:Tomography, Optical Coherence / Q000379:methods / Q000662:veterinary; D014786:Vision Disorders / Q000175:diagnosis / Q000503:physiopathology / Q000662:veterinary*; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields