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The porcine iodoacetic acid model of retinal degeneration: Morpho-functional characterization of the visual system.
Experimental Eye Research ( IF 3.0 ) Pub Date : 2020-02-19 , DOI: 10.1016/j.exer.2020.107979
Francesca Barone 1 , Luisa Vera Muscatello 2 , Domenico Ventrella 2 , Alberto Elmi 2 , Noemi Romagnoli 2 , Luciana Mandrioli 2 , Josè Fernando Maya-Vetencourt 3 , Cristiano Bombardi 2 , Maurizio Mete 4 , Giuseppe Sarli 2 , Fabio Benfenati 5 , Grazia Pertile 4 , Maria Laura Bacci 2
Affiliation  

Porcine models of ophthalmological diseases are often used in pre-clinical translational studies due to pigs' similarities to humans. In particular, the iodoacetic acid (IAA) model of photoreceptor degeneration seems to mimic well the endstage phenotype of human pathologies as retinitis pigmentosa and age-related macular degeneration, with high potential for prosthesis/retinal devices testing. IAA is capable of inducing photoreceptor death by blockage of glycolysis, and its effects on the retina have been described. Nonetheless, up to date, literature lacks of a comprehensive morpho-functional characterization of the entire visual system of this model. This gap is particularly critical for prosthesis testing as inner retinal structures and optic pathways must be preserved to elicit cortical responses and restore vision. In this study, we investigated the functional and anatomical features of the visual system of IAA-treated pigs and compared them to control animals. IAA was administered intravenously at 12 mg/kg; control animals received saline solution (NaCl 0.9% w/v). Electrophysiological analyses included full-field (ffERGs) and pattern (PERGs) electroretinograms and flash visually evoked potentials (fVEPs). Histological evaluations were performed on the retina and the optic pathways and included thickness of the different retinal layers, ganglion cells count, and immunohistochemistry for microglial cells, macroglial cells, and oligodendrocytes. The histological results indicate that IAA treatment does not affect the morphology of the inner retina and optic pathways. Electrophysiology confirms the selective rod and partial cone degeneration, but is ambiguous as to the functionality of the optic pathways, seemingly preserved as indicated by the still detectable fVEPs. Overall, the work ameliorates the characterization of such rapid and cost-effective model, providing more strength and reliability for future pre-clinical translational trials.

中文翻译:

视网膜变性的猪碘乙酸模型:视觉系统的形态功能表征。

由于猪与人的相似性,经常在临床前转化研究中使用眼科疾病的猪模型。特别是,光感受器变性的碘乙酸(IAA)模型似乎很好地模仿了人类病变的晚期表型,如色素性视网膜炎和年龄相关性黄斑变性,具有进行假体/视网膜装置测试的巨大潜力。IAA能够通过阻止糖酵解来诱导光感受器死亡,并且已经描述了其对视网膜的作用。然而,迄今为止,文献缺乏对该模型的整个视觉系统的全面的形态功能描述。对于假体测试来说,这个间隙特别重要,因为必须保留内部视网膜结构和视神经通路,以引起皮层反应并恢复视力。在这个研究中,我们调查了经过IAA处理的猪的视觉系统的功能和解剖特征,并将其与对照动物进行了比较。IAA以12 mg / kg静脉注射;对照动物接受盐溶液(NaCl 0.9%w / v)。电生理分析包括全场(ffERG)和模式(PERG)视网膜电图和闪光视觉诱发电位(fVEP)。对视网膜和视神经通路进行组织学评估,包括不同视网膜层的厚度,神经节细胞计数以及小胶质细胞,大胶质细胞和少突胶质细胞的免疫组织化学。组织学结果表明,IAA治疗不影响内部视网膜和视神经通路的形态。电生理学证实了选择性棒和部分锥体变性,但是对于光通路的功能却模棱两可,似乎仍可检测到的fVEP指出了这一点。总体而言,这项工作改善了这种快速且具有成本效益的模型的特性,为将来的临床前转化试验提供了更大的强度和可靠性。
更新日期:2020-02-20
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