M Dominik Fischer1,2,3, Ditta Zobor4, Georgios A Keliris5, Yibin Shao5, Mathias W Seeliger4, Silke Haverkamp6, Herbert Jägle7, Nikos K Logothetis5, Stelios M Smirnakis5,8. 1. Centre for Ophthalmology, University Eye Hospital, Schleichstr. 12-14, 72076, Tübingen, Germany. Dominik.Fischer@ndcn.ox.ac.uk 2. Institute for Ophthalmic Research, Centre for Ophthalmology, Schleichstr. 12-14, 72076, Tübingen, Germany. Dominik.Fischer@ndcn.ox.ac.uk. 3. 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. 4. Institute for Ophthalmic Research, Centre for Ophthalmology, Schleichstr. 12-14, 72076, Tübingen, Germany. 5. Max-Planck Institute for Biological Cybernetics, Spemannstr. 38-44, 72076, Tübingen, Germany. 6. Neuroanatomy, Max Planck Institute for Brain Research, Deutschordenstr. 46, 60528, Frankfurt a.M., Germany. 7. University Eye Clinic, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany. 8. Department of Neuroscience and Neurology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
Abstract
PURPOSE: 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. CONCLUSION: 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.
PURPOSE: 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. CONCLUSION: 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: Elisabeth M Anger; Angelika Unterhuber; Boris Hermann; Harald Sattmann; Christian Schubert; James E Morgan; Alan Cowey; Peter K Ahnelt; Wolfgang Drexler Journal: Exp Eye Res Date: 2004-06 Impact factor: 3.467
Authors: Gesine Huber; Susanne C Beck; Christian Grimm; Ayse Sahaboglu-Tekgoz; Francois Paquet-Durand; Andreas Wenzel; Peter Humphries; T Michael Redmond; Mathias W Seeliger; M Dominik Fischer Journal: Invest Ophthalmol Vis Sci Date: 2009-08-06 Impact factor: 4.799
Authors: Ala Moshiri; Rui Chen; Soohyun Kim; R Alan Harris; Yumei Li; Muthuswamy Raveendran; Sarah Davis; Qingnan Liang; Ori Pomerantz; Jun Wang; Laura Garzel; Ashley Cameron; Glenn Yiu; J Timothy Stout; Yijun Huang; Christopher J Murphy; Jeffrey Roberts; Kota N Gopalakrishna; Kimberly Boyd; Nikolai O Artemyev; Jeffrey Rogers; Sara M Thomasy Journal: J Clin Invest Date: 2019-01-22 Impact factor: 14.808