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

Detailed functional and structural characterization of a macular lesion in a rhesus macaque.
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DOI:
10.1007/s10633-012-9340-3
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发表时间:
2012-12
期刊:
Documenta ophthalmologica. Advances in ophthalmology
影响因子:
--
通讯作者:
Smirnakis SM
Smirnakis SM
中科院分区:
其他
文献类型:
--
作者:
Dominik Fischer M;Zobor D;Keliris GA;Shao Y;Seeliger MW;Haverkamp S;Jägle H;Logothetis NK;Smirnakis SM

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动物模型是扩大我们对疾病机制的理解和制定未来治疗策略的有力工具。在这里,我们提出了详细的结构和功能研究结果的恒河猴患有自然发生的双侧黄斑营养不良(BMD),部分视神经萎缩和相应的减少中央V1信号在视觉功能磁共振成像实验相比,在一个健康的猕猴(CTRL)的数据相似的年龄。视网膜成像包括红外和自体荧光记录、荧光素和吲哚菁绿色血管造影以及Spectralis HRA + OCT平台上的光谱域光学相干断层扫描(OCT)。视网膜电图包括多焦和Ganzal-ERG记录。处死动物,通过免疫组织化学分析眼睛。血管造影显示受累动物的黄斑血管化减少,黄斑中心凹无血管区(FAZ)显著增大(FAZBMD = 8.85 mm 2 vs. FAZCTRL = 0.32 mm 2)。OCT显示FAZ内双侧黄斑变薄(总视网膜厚度,TRTBMD = 174 ± 9 μm)和部分视神经萎缩(TRTCTRL = 303 ± 45 μm)。分割分析显示,视网膜内层主要受到影响(内部视网膜厚度,IRTBMD = 33 ± 9 μm vs. IRTCTRL = 143 ± 45 μm),而外部视网膜基本上保持其厚度(ORTBMD = 141 ± 7 μm vs. ORTCTRL = 160 ± 11 μm)。黄斑形态的改变对应于多焦视网膜电图中中央信号的优先减少和甘兹菲尔德视网膜电图中视锥细胞源性反应的特定衰减,而视杆细胞功能保持正常。我们提供了灵长类动物黄斑疾病的详细特征。本研究旨在激发对患有黄斑疾病的灵长类动物的认识和进一步调查,最终导致灵长类动物模型的鉴定,并促进治疗策略的临床前开发。
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 auto fluorescence 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 = 8.85 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. 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.
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