Characterization of photoreceptor degeneration in the rhodopsin P23H transgenic rat line 2 using optical coherence tomography.

Characterization of photoreceptor degeneration in the rhodopsin P23H transgenic rat line 2 using optical coherence tomography.
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DOI:
10.1371/journal.pone.0193778
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Nakazawa M
Nakazawa M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Monai N;Yamauchi K;Tanabu R;Gonome T;Ishiguro SI;Nakazawa M

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表征红紫质P23H转基因大鼠(线2)的光感受器变性的光学相干断层扫描(OCT)外观与组织学,超微结构和视网膜电图(ERG)结果的关系。采用纯合子视紫红质P23H转基因白化大鼠(2号线,极慢变性模型)。使用OCT (Micron IV®;Phoenix Research Labs, Pleasanton, CA, USA),记录从出生后第15天到第287天的光感受器变性的自然过程。通过与p62和p169的组织学和超微结构结果比较,对OCT图像进行定性观察。此外,定量分析变性过程中视网膜各层的纵向变化,并与野生型SD大鼠进行比较。并分析了ERG(全视野联合杆锥反应,3.0 cds/m2刺激)结果与OCT图像之间的关系。在定性研究中,P23H大鼠在PN第32天鉴定出两层可能对应于光感受器内节段椭球区(EZ)和指间区(IZ)。然而,p46后OCT感光器内外段(IS/OS)层呈弥漫性高反射,在OCT上已无法识别EZ和IZ区。相比之下,SD大鼠的EZ和IZ区至少在p247前仍能清晰区分。超微结构研究显示P23H大鼠在p62时光感受器外节盘部分紊乱,但光镜组织学研究几乎未发现外节异常。在定量研究中,p71后P23H大鼠的视网膜外层包括外丛状层(OPL)和外核层(ONL)明显变薄。P23H组大鼠的IS/OS层厚度保持到p130, p237组大鼠IS/OS层厚度较SD大鼠明显变薄。ERG a波和b波振幅的纵向衰减与OPL和ONL复合层的厚度显著相关,而与IS/OS层的厚度无关。OCT显示红紫质P23H转基因大鼠(line 2)退行性光感受器IS/OS层为弥漫性高反射区,即使在早期也是如此,超微结构评估可识别部分紊乱和不稳定的OS盘,但组织学研究无法识别。P23H大鼠a波和b波的振幅主要取决于OPL和ONL层的厚度,而不是光感受器IS/OS层的厚度。
To characterize the optical coherence tomography (OCT) appearances of photoreceptor degeneration in the rhodopsin P23H transgenic rat (line 2) in relation to the histological, ultrastructural, and electroretinography (ERG) findings. Homozygous rhodopsin P23H transgenic albino rats (line 2, very-slow degeneration model) were employed. Using OCT (Micron IV®; Phoenix Research Labs, Pleasanton, CA, USA), the natural course of photoreceptor degeneration was recorded from postnatal day (P) 15 to P 287. The OCT images were qualitatively observed by comparing them to histological and ultrastructural findings at P 62 and P 169. In addition, each retinal layer was quantitatively analyzed longitudinally during degeneration, compared it to that observed in wild type Sprague-Dawley (SD) rats. The relationships between the ERG (full-field combined rod-cone response, 3.0 cds/m2 stimulation) findings and OCT images were also analyzed. In the qualitative study, the two layers presumably corresponding to the photoreceptor inner segment ellipsoid zone (EZ) and interdigitation zone (IZ) were identified in the P23H rat until PN day 32. However, the photoreceptor inner and outer segment (IS/OS) layer became diffusely hyperreflective on OCT after P 46, and the EZ and IZ zones could no longer be identified on OCT. In contrast, in the SD rats, the EZ and IZ were clearly distinguished until at least P 247. The ultrastructural study showed partial disarrangements of the photoreceptor outer segment discs in the P23H rats at P 62, although a light-microscopic histological study detected almost no abnormality in the outer segment. In the quantitative study, the outer retinal layer including the outer plexiform layer (OPL) and the outer nuclear layer (ONL) became significantly thinner in the P23H rats than in the SD rats after P 71. The thickness of the IS/OS layer was maintained in the P23H rats until P 130, and it became statistically thinner than in the SD rats at P 237. The longitudinal attenuation in the amplitude of the a- and b-waves of ERG was significantly correlated with the thickness of the combined OPL and ONL but not with that of the IS/OS layer. OCT showed the degenerated photoreceptor IS/OS layer in rhodopsin P23H transgenic rats (line 2) as a diffuse hyperreflective zone, even in the early stage, with the partially disarranged and destabilized OS discs recognizable by ultrastructural assessment but not by a histological study. The amplitude of the a- and b-waves mainly depends on the thickness of the OPL and ONL layer rather than the thickness of the photoreceptor IS/OS layer in P23H rats.
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