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眼压夹闭导致眼灌注时一氧化氮介导的清除。

Pressure Clamping During Ocular Perfusions Drives Nitric Oxide-Mediated Washout.

机构信息

Ophthalmology Department, Duke University, Durham, North Carolina, United States.

Ophthalmology Department, University of Utah, Utah, United States.

出版信息

Invest Ophthalmol Vis Sci. 2023 Jun 1;64(7):36. doi: 10.1167/iovs.64.7.36.

DOI:10.1167/iovs.64.7.36
PMID:37358489
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10297780/
Abstract

PURPOSE

The aim of this study was to test the hypothesis that nitric oxide (NO) mediates a pressure-dependent, negative feedback loop that maintains conventional outflow homeostasis and thus IOP. If true, holding pressure during ocular perfusions will result in uncontrolled production of NO, hyper-relaxation of the trabecular meshwork, and washout.

METHODS

Paired porcine eyes were perfused at constant pressure of 15 mm Hg. After 1 hour acclimatization, one eye was exchanged with N5-[imino(nitroamino)methyl]-L-ornithine, methyl ester, monohydrochloride (L-NAME) (50 µm) and the contralateral eye with DBG, and perfused for 3 hours. In a separate group, one eye was exchanged with DETA-NO (100 nM) and the other with DBG and perfused for 30 minutes. Changes in conventional outflow tissue function and morphology were monitored.

RESULTS

Control eyes exhibited a washout rate of 15% (P = 0.0026), whereas eyes perfused with L-NAME showed a 10% decrease in outflow facility from baseline over 3 hours (P < 0.01); with nitrite levels in effluent positively correlating with time and facility. Compared with L-NAME-treated eyes, significant morphological changes in control eyes included increased distal vessel size, number of giant vacuoles, and juxtacanalicular tissue separation from the angular aqueous plexi (P < 0.05). For 30-minute perfusions, control eyes showed a washout rate of 11% (P = 0.075), whereas DETA-NO-treated eyes showed an increased washout rate of 33% from baseline (P < 0.005). Compared with control eyes, significant morphological changes in DETA-NO-treated eyes also included increased distal vessel size, number of giant vacuoles and juxtacanalicular tissue separation (P < 0.05).

CONCLUSIONS

Uncontrolled NO production is responsible for washout during perfusions of nonhuman eyes where pressure is clamped.

摘要

目的

本研究旨在验证假设，即一氧化氮（NO）介导一种压力依赖性的负反馈回路，维持传统的房水流出稳态和眼压（IOP）。如果这是正确的，在眼部灌注期间保持压力将导致不受控制的 NO 产生、小梁网过度松弛和冲洗。

方法

对配对的猪眼以 15mmHg 的恒定压力进行灌注。在 1 小时适应期后，一只眼用 N5-[亚氨基（硝基氨基）甲基]-L-鸟氨酸，甲酯，单盐酸盐（L-NAME）（50µM）交换，对侧眼用 DBG 交换，并灌注 3 小时。在另一组中，一只眼用 DETA-NO（100nM）交换，另一只眼用 DBG 交换并灌注 30 分钟。监测传统房水流出组织功能和形态的变化。

结果

对照眼表现出 15%的冲洗率（P=0.0026），而用 L-NAME 灌注的眼在 3 小时内从基线流出率下降 10%（P<0.01）；流出物中的亚硝酸盐水平与时间和流出率呈正相关。与 L-NAME 处理的眼相比，对照眼的显著形态变化包括远端血管大小增加、巨空泡数量增加以及房角水丛与近小管组织分离（P<0.05）。对于 30 分钟的灌注，对照眼的冲洗率为 11%（P=0.075），而 DETA-NO 处理的眼的冲洗率从基线增加了 33%（P<0.005）。与对照眼相比，DETA-NO 处理的眼也有明显的形态变化，包括远端血管大小增加、巨空泡数量增加和近小管组织分离（P<0.05）。

结论

在非人类眼睛的灌注中，当压力被钳制时，不受控制的 NO 产生是冲洗的原因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cc4/10297780/c0266f0794e3/iovs-64-7-36-f008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cc4/10297780/ec147563d8f3/iovs-64-7-36-f001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cc4/10297780/c253725ff20b/iovs-64-7-36-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cc4/10297780/d38ba66639a4/iovs-64-7-36-f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cc4/10297780/348c3ba741c7/iovs-64-7-36-f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cc4/10297780/c0266f0794e3/iovs-64-7-36-f008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cc4/10297780/ec147563d8f3/iovs-64-7-36-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cc4/10297780/731d6af7beb1/iovs-64-7-36-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cc4/10297780/7b436e372e76/iovs-64-7-36-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cc4/10297780/ebbbbbcc6aef/iovs-64-7-36-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cc4/10297780/c253725ff20b/iovs-64-7-36-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cc4/10297780/d38ba66639a4/iovs-64-7-36-f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cc4/10297780/348c3ba741c7/iovs-64-7-36-f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cc4/10297780/c0266f0794e3/iovs-64-7-36-f008.jpg

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