Mechanism for Altered Dark-Adapted Electroretinogram Responses in DBA/2J Mice Includes Pupil Dilation Deficits.
Mechanism for Altered Dark-Adapted Electroretinogram Responses in DBA/2J Mice Includes Pupil Dilation Deficits.
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DOI：
10.1080/02713683.2022.2044055
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发表时间：
2022-06
影响因子：
2
通讯作者：
中科院分区：
文献类型：
--
作者：
DBA/2J(D2)小鼠是一种已建立的色素性青光眼模型，是一种原发性开角型青光眼。以前的研究已经证明D2小鼠的闪光视网膜电信号(ERG)反应存在缺陷，但这些缺陷的来源尚不清楚。本研究的目的是了解D2ERG中这些A波和B波变化的起源。为了实现这一点，我们分析了9个月大的DBA/2J-GPNMB+(D2-对照)和D2小鼠眼睛在ERG反应、眼压(IOP)、外核层厚度和瞳孔面积方面的差异。D2暗视ERG显示A波振幅降低，潜伏期延长，强度-反应曲线明显右移。D2眼压在大约7个月龄时升高，并且与ERG A波敏感度有微弱的相关性。与D2对照视网膜相比，D2s组视网膜外核层厚度无显著差异。经托吡卡胺滴眼液治疗后，D2小鼠的瞳孔形态也出现异常，无扩张。瞳孔大小与A波敏感性中等相关，在给予匹罗卡品收缩瞳孔后，这一点在C57BL/6J小鼠身上得到了药理学上的复制。然而，匹罗卡品治疗并不影响ERG波幅。这些数据表明，较小的瞳孔大小阻止了光线到达光感受器，从而导致D2小鼠的ERG敏感性降低。D2小鼠的ERG A波幅度降低可能是由于光感受器反应功能障碍所致。
The DBA/2J (D2) mouse is an established model of pigmentary glaucoma, a type of primary open angle glaucoma. Prior studies have documented defects in flash electroretinogram (ERG) responses in D2 mice, but the origin of those defects is not clear. The purpose of this study was to understand the origin of these A-wave and B-wave changes in D2 ERGs. To accomplish this, we analyzed the differences between 9-month-old DBA/2J-Gpnmb+ (D2-control) and D2 mouse eyes in relation to ERG responses, intraocular pressure (IOP), outer nuclear layer thickness, and pupil area. D2 scotopic ERGs showed lower A-wave amplitude and longer implicit time as well as a significant rightward shift in the intensity-response curve. D2 IOP increased at approximately seven months of age and had a weak correlation with the ERG A-wave sensitivity. Outer nuclear layer thickness was not significantly different in D2s compared to D2-control retinas. D2 mouse pupils also showed abnormal pupillary shape and no dilation following treatment with tropicamide eye drops. The pupil size moderately correlated with the A-wave sensitivity and this was pharmacologically replicated in C57Bl/6J mice following administration of pilocarpine to constrict the pupils. However, pilocarpine treatment did not affect ERG amplitudes. These data suggest that the smaller pupil sizes prevented light from reaching the photoreceptors and thus contributed to reduced ERG sensitivity in D2 mice. The reduced ERG A-wave amplitude in D2 mice likely results from dysfunctional photoreceptor responses.
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影响因子：
4.4
作者：
Fernandez-Sanchez, Laura;de Sevilla Mueller, Luis Perez;Cuenca, Nicolas
通讯作者：
Cuenca, Nicolas
影响因子：
4.4
作者：
Leung, Christopher Kai-shun;Cheung, Carol Yim-lui;Weinreb, Robert N.
通讯作者：
Weinreb, Robert N.
视网膜神经节细胞变性是拓扑的，但在DBA/2J小鼠中不是特异性细胞类型。
影响因子：
7.8
作者：
Jakobs, Tatjana C;Libby, Richard T;Ben, Yixin;John, Simon W M;Masland, Richard H
通讯作者：
Masland, Richard H
影响因子：
8.8
作者：
Care RA;Anastassov IA;Kastner DB;Kuo YM;Della Santina L;Dunn FA
通讯作者：
Dunn FA
影响因子：
3.4
作者：
Porciatti V
通讯作者：
Porciatti V