脉络膜血流动态调节功能障碍及交感神经切断术后脉络膜视网膜功能和病理改变

Defective Choroidal Blood Flow Baroregulation and Retinal Dysfunction and Pathology Following Sympathetic Denervation of Choroid.

机构信息

Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee, United States.

Department of Ophthalmology, University of Tennessee, Memphis, Tennessee, United States.

出版信息

Invest Ophthalmol Vis Sci. 2018 Oct 1;59(12):5032-5044. doi: 10.1167/iovs.18-24954.

DOI:10.1167/iovs.18-24954

PMID:30326072

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6190756/

Abstract

PURPOSE

We sought to determine if sympathetic denervation of choroid impairs choroidal blood flow (ChBF) regulation and harms retina.

METHODS

Rats received bilateral superior cervical ganglionectomy (SCGx), which depleted choroid of sympathetic but not parasympathetic innervation. The flash-evoked scotopic ERG and visual acuity were measured 2 to 3 months after SCGx, and vasoconstrictive ChBF baroregulation during high systemic arterial blood pressure (ABP) induced by LNAME was assessed by laser Doppler flowmetry (LDF). Eyes were harvested for histologic evaluation.

RESULTS

ChBF increased in parallel with ABP in SCGx rats over an ABP range of 90% to 140% of baseline ABP, while in sham rats ChBF remained stable and uncorrelated with ABP. ERG a- and b-wave latencies and amplitudes, and visual acuity were significantly reduced after SCGx. In SCGx retina, Müller cell GFAP immunolabeling was upregulated 2.5-fold, and Iba1+ microglia were increased 3-fold. Dopaminergic amacrine cell fibers in inner plexiform layer were reduced in SCGx rats, and photoreceptors were slightly depleted. Functional deficits and pathology were correlated with impairments in sympathetic regulation of ChBF.

CONCLUSIONS

These studies indicate that sympathetic denervation of choroid impairs ChBF baroregulation during elevated ABP, leading to choroidal overperfusion. This defect in ChBF regulation is associated with impaired retinal function and retinal pathology. As sympathetic ChBF baroregulatory defects have been observed in young individuals with complement factor H (CFH) polymorphisms associated with risk for AMD, our results suggest these defects may harm retina, perhaps contributing to AMD pathogenesis.

摘要

目的

我们旨在确定脉络膜的交感神经去神经支配是否会损害脉络膜血流（ChBF）调节并损害视网膜。

方法

大鼠接受双侧颈上交感神经节切除术（SCGx），这会耗尽脉络膜的交感神经但不会耗尽副交感神经支配。在 SCGx 后 2 至 3 个月测量闪光诱发的暗视视网膜电图和视力，并通过激光多普勒血流计（LDF）评估在 LNAME 诱导的高全身动脉血压（ABP）下的血管收缩性 ChBF 血压调节。采集眼球进行组织学评估。

结果

在 SCGx 大鼠中，ChBF 在 ABP 范围内从基线 ABP 的 90%增加到 140%，与 ABP 平行增加，而在假手术大鼠中，ChBF 保持稳定且与 ABP 无关。在 SCGx 后，ERG a 和 b 波潜伏期和幅度以及视力明显降低。在 SCGx 视网膜中，Müller 细胞 GFAP 免疫标记物上调 2.5 倍，Iba1+小胶质细胞增加 3 倍。SCGx 大鼠内丛状层中的多巴胺能无长突细胞纤维减少，光感受器略有耗竭。功能缺陷和病理学与 ChBF 交感调节受损相关。

结论

这些研究表明，脉络膜的交感神经去神经支配会损害升高 ABP 期间的 ChBF 血压调节，导致脉络膜过度灌注。这种 ChBF 调节缺陷与视网膜功能和视网膜病理学受损有关。由于在与 AMD 风险相关的补体因子 H（CFH）多态性的年轻个体中观察到交感神经 ChBF 血压调节缺陷，我们的结果表明这些缺陷可能会损害视网膜，也许有助于 AMD 的发病机制。