Retinal Responses to Visual Stimuli in Interphotoreceptor Retinoid Binding-Protein Knock-Out Mice.

Retinal Responses to Visual Stimuli in Interphotoreceptor Retinoid Binding-Protein Knock-Out Mice.
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DOI:
10.3390/ijms241310655
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发表时间:
2023-06-26
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
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光感受器间视黄醇结合蛋白(IRBP)是视网膜下腔中丰富的糖蛋白,与光感受器(PR)外节和视网膜色素上皮(RPE)的突起结合。 IRBP 结合类视黄醇,包括 11-顺式视黄醛和全反式视黄醇。在这项研究中,评估了 IRBP 敲除 (KO) 小鼠执行高要求视觉任务的视觉功能。令人惊讶的是,与野生型 (WT) 相比,IRBP KO 小鼠的暗视临界闪烁频率 (CFF) 没有差异。然而,它们的明视 CFF 确实比 WT 低。与 WT 相比,IRBP KO 小鼠的暗视和明视敏锐度以及对比敏感度降低。与 WT 相比,IRBP KO 小鼠的外核层 (ONL) 厚度、PR 外节和内节以及全视网膜厚度 (FRT) 显着减少。 IRBP KO 小鼠中的视锥细胞较少。总体而言,这些结果证实了 30 天内视杆细胞的大量损失和视锥细胞的大量损失。缺乏 IRBP 会导致锥体电路损坏,从而降低明视觉闪烁、对比敏感度和空间频率敏感度。 c 波响应明亮的光阶而减少并加速。该结果还表明视网膜色素上皮活性发生改变。似乎存在一种补偿机制,例如 PR 和双极细胞之间更高的突触增益,因为 b 波的损失并不线性跟随杆状细胞或 a 波的损失。尽管 IRBP KO 小鼠 ONL 变薄且暗视视网膜电图 (ERG) 减少,但暗视 CFF 仍正常,这表明即使在视杆细胞大量丢失的情况下,检测(编码)阈值暗视闪烁的电路也存在冗余或可塑性。
Interphotoreceptor retinoid-binding protein (IRBP) is an abundant glycoprotein in the subretinal space bound by the photoreceptor (PR) outer segments and the processes of the retinal pigmented epithelium (RPE). IRBP binds retinoids, including 11-cis-retinal and all-trans-retinol. In this study, visual function for demanding visual tasks was assessed in IRBP knock-out (KO) mice. Surprisingly, IRBP KO mice showed no differences in scotopic critical flicker frequency (CFF) compared to wildtype (WT). However, they did have lower photopic CFF than WT. IRBP KO mice had reduced scotopic and photopic acuity and contrast sensitivity compared to WT. IRBP KO mice had a significant reduction in outer nuclear layer (ONL) thickness, PR outer and inner segment, and full retinal thickness (FRT) compared to WT. There were fewer cones in IRBP KO mice. Overall, these results confirm substantial loss of rods and significant loss of cones within 30 days. Absence of IRBP resulted in cone circuit damage, reducing photopic flicker, contrast sensitivity, and spatial frequency sensitivity. The c-wave was reduced and accelerated in response to bright steps of light. This result also suggests altered retinal pigment epithelium activity. There appears to be a compensatory mechanism such as higher synaptic gain between PRs and bipolar cells since the loss of the b-wave did not linearly follow the loss of rods, or the a-wave. Scotopic CFF is normal despite thinning of ONL and reduced scotopic electroretinogram (ERG) in IRBP KO mice, suggesting either a redundancy or plasticity in circuits detecting (encoding) scotopic flicker at threshold even with substantial rod loss.
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