Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky, United States.
Invest Ophthalmol Vis Sci. 2014 Apr 17;55(4):2460-8. doi: 10.1167/iovs.13-13724.
Human and swine retinas have morphological and functional similarities. In the absence of primate models, the swine is an attractive model to study retinal function and disease, with its cone-rich visual streak, our ability to manipulate their genome, and the differences in susceptibility of rod and cone photoreceptors to disease. We characterized the normal development of cone function and its subsequent decline in a P23H rhodopsin transgenic (TgP23H) miniswine model of autosomal dominant RP.
Semen from TgP23H miniswine 53-1 inseminated domestic swine and produced TgP23H and Wt hybrid littermates. Retinal function was evaluated using ERGs between postnatal days (P) 14 and 120. Retinal ganglion cell (RGC) responses were recorded to full-field stimuli at several intensities. Retinal morphology was assessed using light and electron microscopy.
Scotopic retinal function matures in Wt pigs up to P60, but never develops in TgP23H pigs. Wt and TgP23H photopic vision matures similarly up to P30 and diverges at P60 where TgP23H cone vision declines. There are fewer TgP23H RGCs with visually evoked responses at all ages and their response to light is compromised. Photoreceptor morphological changes mirror these functional changes.
Lack of early scotopic function in TgP23H swine suggests it as a model of an aggressive form of RP. In this mammalian model of RP, normal cone function develops independent of rod function. Therefore, its retina represents a system in which therapies to rescue cones can be developed to prolong photopic visual function in RP patients.
人类和猪的视网膜在形态和功能上具有相似性。在没有灵长类动物模型的情况下，猪是研究视网膜功能和疾病的理想模型，因为它具有富含视锥细胞的视觉纹、我们能够操纵其基因组的能力，以及视杆细胞和视锥细胞对疾病易感性的差异。我们对 P23H 视蛋白转基因（TgP23H）小型猪常染色体显性遗传性 RP 模型中视锥细胞功能的正常发育及其随后的衰退进行了特征描述。
将 TgP23H 小型猪精液进行人工授精，使其与家猪交配，产生 TgP23H 和 WT 杂交幼崽。在出生后第 14 天至 120 天之间使用 ERG 评估视网膜功能。使用全视野刺激记录视网膜神经节细胞（RGC）的反应，刺激强度不同。使用光镜和电镜评估视网膜形态。
WT 猪的暗视视网膜功能在 P60 之前成熟，但 TgP23H 猪的功能从未发育。WT 和 TgP23H 的明视视觉在 P30 之前发育相似，然后在 P60 时出现差异，此时 TgP23H 的视锥细胞视觉下降。在所有年龄段，TgP23H 的 RGC 数量较少，并且对光的反应受到损害。光感受器形态变化反映了这些功能变化。
TgP23H 小型猪缺乏早期暗视功能，提示其为一种侵袭性 RP 模型。在这种哺乳动物 RP 模型中，视锥细胞功能的正常发育独立于视杆细胞功能。因此，其视网膜代表了一个系统，在此系统中，可以开发拯救视锥细胞的疗法，以延长 RP 患者的明视视觉功能。
