Measurement of postmortem outflow facility using iPerfusion.
Measurement of postmortem outflow facility using iPerfusion.
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DOI：
10.1016/j.exer.2022.109103
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发表时间：
2022-07
影响因子：
3.4
通讯作者：
van Batenburg-Sherwood, Joseph
中科院分区：
文献类型：
--
作者：
Madekurozwa, Michael;Reina-Torres, Ester;Overby, Darryl R.;van Batenburg-Sherwood, Joseph
青光眼的关键危险因素是眼内压（IOP）升高，缓解眼压是抑制视力进一步丧失的唯一有效治疗方法。 IOP 受房水流经抵抗性组织的流动调节，流出设施 C 的减少是青光眼中 IOP 升高的原因。因此，在研究青光眼的病理生理学和测试降低 IOP 的候选治疗方法时，C 的测量非常重要。由于相似的解剖结构和对药物治疗的反应，小鼠眼睛是人类房水动力学的常见模型。离体制剂，其中将去核的小鼠眼睛安装在温度控制浴中并插管，已得到很好的表征并被广泛使用。死后原位模型（眼睛在尸体内灌注）受到的关注相对较少。在这项研究中，我们使用 iPerfusion 系统研究了死后原位模型，特别关注 i) 是否存在与压力无关的流量，ii) 蒸发对测量流量的影响，以及 iii) 流出设施的大小和压力依赖性以及这些属性如何受到死后变化的影响。插管后立即进行的测量和多压力设施测量表明，死后眼睛中的压力无关流量可以忽略不计，这与之前研究中的假设相反。使用湿度室，我们研究了周围空气的湿度是否会影响测量的流量。我们发现，在室内湿度水平下，眼睛上的盐水滴蒸发会产生与流出量相当的人为流量，而高相对湿度（> 85％）环境会消除这种流量。平均死后流出设施约为 4 nl/min/mmHg，与离体观察到的值相似，无论插管前是否引入死后延迟。相对于之前的离体数据，测量的流出设施值的动物内变异性也减少了。相对于离体模型，在尸检中流出设施的压力依赖性降低，并且当安乐死后 > 40 分钟对眼睛进行插管时，流出设施的压力依赖性实际上被消除。总的来说，我们的结果表明，当实验条件得到适当控制时，与死后灌注相关的技术复杂性的适度增加可减少流出设施的变异性和压力依赖性。
The key risk factor for glaucoma is elevation of intraocular pressure (IOP) and alleviating it is the only effective therapeutic approach to inhibit further vision loss. IOP is regulated by the flow of aqueous humour across resistive tissues, and a reduction in outflow facility C, is responsible for the IOP elevation in glaucoma. Measurement of C is therefore important when investigating the pathophysiology of glaucoma and testing candidate treatments for lowering IOP. Due to similar anatomy and response to pharmacological treatments, mouse eyes are a common model of human aqueous humour dynamics. The ex vivo preparation, in which an enucleated mouse eye is mounted in a temperature controlled bath and cannulated, has been well characterised and is widely used. The postmortem in situ model, in which the eyes are perfused within the cadaver, has received relatively little attention. In this study, we investigate the postmortem in situ model using the iPerfusion system, with a particular focus on i) the presence or absence of pressure-independent flow, ii) the effect of evaporation on measured flow rates and iii) the magnitude and pressure dependence of outflow facility and how these properties are affected by postmortem changes. Measurements immediately after cannulation and following multi-pressure facility measurement demonstrated negligible pressure-independent flow in postmortem eyes, in contrast to assumptions made in previous studies. Using a humidity chamber, we investigated whether the humidity of the surrounding air would influence measured flow rates. We found that at room levels of humidity, evaporation of saline droplets on the eye resulted in artefactual flow rates with a magnitude comparable to outflow, which were eliminated by a high relative humidity (>85%) environment. Average postmortem outflow facility was ~4 nl/min/mmHg, similar to values observed ex vivo, irrespective of whether a postmortem delay was introduced prior to cannulation. The intra-animal variability of measured outflow facility values was also reduced relative to previous ex vivo data. The pressure-dependence of outflow facility was reduced in the postmortem relative to ex vivo model, and practically eliminated when eyes were cannulated > 40 minutes after euthanisation. Overall, our results indicate that the moderately increased technical complexity associated with postmortem perfusion provides reduced variability and reduced pressure-dependence in outflow facility, when experimental conditions are properly controlled.
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影响因子：
3
作者：
Wisard, Jeffrey;Chrenek, Micah A.;Wright, Charles;Dalal, Nupur;Pardue, Machelle T.;Boatright, Jeffrey H.;Nickerson, John M.
通讯作者：
Nickerson, John M.
DOI：
10.1096/fj.202000702rr
发表时间：
2020-08
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Li G;Schmitt H;Johnson WM;Lee C;Navarro I;Cui J;Fleming T;Gomez-Caraballo M;Elliott MH;Sherwood JM;Hauser MA;Farsiu S;Ethier CR;Stamer WD
通讯作者：
Stamer WD
褐-诺威大鼠的水液动力学
影响因子：
4.4
作者：
Ficarrotta, Kayla R.;Bello, Simon A.;Passaglia, Christopher L.
通讯作者：
Passaglia, Christopher L.
影响因子：
3.4
作者：
Johnson M;McLaren JW;Overby DR
通讯作者：
Overby DR
影响因子：
3.5
作者：
Li, LY;Tighe, BJ;Ruberti, JW
通讯作者：
Ruberti, JW