TY - JOUR
T1 - Detailed functional and structural characterization of a macular lesion in a rhesus macaque
AU - Dominik Fischer, M.
AU - Zobor, Ditta
AU - Keliris, Georgios A.
AU - Shao, Yibin
AU - Seeliger, Mathias W.
AU - Haverkamp, Silke
AU - Jägle, Herbert
AU - Logothetis, Nikos K.
AU - Smirnakis, Stelios M.
N1 - R01 EY019272, NEI NIH HHS, United States
PY - 2012/12
Y1 - 2012/12
N2 - 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 vascularizationwith significantly larger foveal avascular zones (FAZ) in the affected animal (FAZBMD = 8.85 mm2 vs. FAZCTRL = 0.32 mm2). 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. © Springer-Verlag 2012.
AB - 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 vascularizationwith significantly larger foveal avascular zones (FAZ) in the affected animal (FAZBMD = 8.85 mm2 vs. FAZCTRL = 0.32 mm2). 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. © Springer-Verlag 2012.
KW - Electroretinography
KW - Functional MRI
KW - Macular disorder
KW - Neurodegeneration
KW - Optical coherence tomography
U2 - 10.1007/s10633-012-9340-3
DO - 10.1007/s10633-012-9340-3
M3 - Article
C2 - 22923360
SN - 0012-4486
VL - 125
SP - 179
EP - 194
JO - Documenta Ophthalmologica
JF - Documenta Ophthalmologica
IS - 3
ER -