Department of Optometry and Vision Science, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Int J Mol Sci. 2023 Jun 26;24(13):10655. doi: 10.3390/ijms241310655.
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.
光感受器间维生素 A 结合蛋白（IRBP）是一种丰富的糖蛋白，位于视网膜色素上皮（RPE）的光感受器（PR）外节和突起之间的视网膜下空间。IRBP 结合视黄醛，包括 11-顺式视黄醛和全反式视黄醇。在这项研究中，评估了缺乏 IRBP 的小鼠（IRBP KO 小鼠）对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 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较低。与 WT 相比，IRBP KO 小鼠的外核层（ONL）厚度、PR 外节和内节以及整个视网膜厚度（FRT）减少。IRBP KO 小鼠中的视锥细胞数量减少。总的来说，这些结果证实了在 30 天内大量的视杆细胞和显著的视锥细胞丧失。IRBP 的缺失导致视锥细胞电路损伤，降低了明视闪烁、对比敏感度和空间频率敏感度。c 波的减少和对明亮光阶的快速反应表明视色素上皮活动发生改变。似乎存在一种代偿机制，例如 PR 和双极细胞之间更高的突触增益，因为 b 波的丧失并没有与视杆细胞的丧失或 a 波线性相关。尽管 IRBP KO 小鼠的 ONL 变薄，暗视视网膜电图（ERG）减少，但暗视 CFF 正常，这表明在即使有大量视杆细胞丧失的情况下，检测（编码）暗视闪烁的电路存在冗余或可塑性。
