Detailed functional and structural characterization of a macular lesion in a rhesus macaque

Abstract

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. 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. Angiography showed reduced macular vascularization with significantly larger foveal avascular zones (FAZ) in the affected animal (FAZBMD=8.85mm(2) vs. FAZCTRL=0.32mm(2)). OCT showed bilateral thinning of the macula within the FAZ (total retinal thickness, TRTBMD=174±9µm) and partial optic nerve atrophy when compared to control (TRTCTRL=303±45µm). Segmentation analysis revealed that inner retinal layers were primarily affected (inner retinal thickness, IRTBMD=33±9µm vs. IRTCTRL=143±45µm), while the outer retina essentially maintained its thickness (ORTBMD=141±7µm vs. ORTCTRL=160±11µm). 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. 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.