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Invest Ophthalmol Vis Sci. 2020 Jun 3;61(6):6. doi: 10.1167/iovs.61.6.6.
The majority of small animal species used in research are nocturnal, with retinae that are anatomically and functionally dissimilar from humans, complicating their use as disease models. Herein we characterize the retinal structure and electrophysiological function of the diurnal, cone-dominant 13-lined ground squirrel (13-LGS) retina during euthermia and in hibernation.
Full-field electroretinography (ERG) was performed in 13-LGS and Brown Norway (BN) rat models to establish baseline values for retinal function in each species, including following intravitreal injection of pharmacologic agents to selectively block the contributions of ON- and OFF-bipolar cells. The effect of hibernation-associated retinal remodeling on electrophysiological function was assessed in 13-LGS during torpor and emergence, with correlative histology performed using transmission electron microscopy.
Under light-adapted conditions, the a-, b-, and d-wave amplitude of the 13-LGS was significantly greater than that of the BN rat. Retinal function was absent in the 13-LGS during hibernation and correlated to widespread disruption of photoreceptor and RPE structure. Remarkably, both retinal function and structure recovered rapidly on emergence from hibernation, with ERG responses reaching normal amplitude within 6 hours.
ERG responses for both BN rats and 13-LGS reflect the relative proportions of cone photoreceptors present within the retinae, indicating that the cone-dominant 13-LGS may be a potentially useful model for studying human central retinal function and disease. That retinal remodeling and restoration of electrophysiological function occurs rapidly on emergence from hibernation implies the 13-LGS may also be a useful tool for studying aspects of retinal physiology and recovery from injury.
大多数用于研究的小型动物物种都是夜间活动的,其视网膜在解剖结构和功能上与人类不同,这使得它们难以作为疾病模型。在此,我们描述了昼行性、以视锥细胞为主的 13 线地松鼠(13-LGS)视网膜在体温正常和冬眠期间的视网膜结构和电生理功能。
在 13-LGS 和棕褐色挪威(BN)大鼠模型中进行全视野视网膜电图(ERG),以建立每种物种视网膜功能的基线值,包括在玻璃体内注射药物选择性阻断 ON 和 OFF 双极细胞的贡献后。在 13-LGS 冬眠期间和苏醒期间评估与冬眠相关的视网膜重塑对电生理功能的影响,并通过透射电子显微镜进行相关的组织学研究。
在明适应条件下,13-LGS 的 a、b 和 d 波振幅明显大于 BN 大鼠。13-LGS 在冬眠期间没有视网膜功能,与光感受器和 RPE 结构的广泛破坏有关。值得注意的是,从冬眠中苏醒后,视网膜功能和结构迅速恢复,ERG 反应在 6 小时内恢复正常幅度。
BN 大鼠和 13-LGS 的 ERG 反应反映了视网膜中存在的视锥细胞的相对比例,表明以视锥细胞为主的 13-LGS 可能是研究人类中央视网膜功能和疾病的潜在有用模型。从冬眠中苏醒后,视网膜重塑和电生理功能的恢复迅速,这意味着 13-LGS 也可能是研究视网膜生理学和从损伤中恢复的有用工具。