Pupillary reflex and behavioral masking responses to light as functional measures of retinal degeneration in mice.
Pupillary reflex and behavioral masking responses to light as functional measures of retinal degeneration in mice.
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DOI：
10.1371/journal.pone.0244702
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Thompson S
中科院分区：
文献类型：
--
作者：
Contreras EO;Dearing CG;Ashinhurst CA;Fish BA;Hossain SN;Rey AM;Silva PD;Thompson S
视网膜病理和治疗效果的临床前测试取决于可靠和有效的视网膜功能测量。视网膜电图（ERG）和视敏度测试是理想的标准，但在有用视力仍然存在时可能无法测量。对光的非成像反应，如瞳孔光反射（PLR）是有吸引力的替代品。然而，目前尚不清楚这些反应如何准确地反映特定疾病模型中视觉能力的变化。本研究的目的是测试是否措施的非视觉反应的光与先前确定的视觉功能在两个感光细胞变性。在具有完整视网膜内回路的3月龄野生型小鼠（WT）、具有早期和快速视杆细胞和视锥细胞损失的Pde 6 b-rd 1/rd 1小鼠（rd 1）以及具有较慢进行性视杆细胞和视锥细胞损失的Prph 2-Rd 2/Rd 2小鼠（Rd 2）中测量掩蔽行为（光诱导的转轮活动变化）和PLR的敏感性。在rd 1小鼠中，阴性掩蔽的敏感性增加，阳性掩蔽不存在，PLR的敏感性严重降低。在Rd 2小鼠中，阳性掩蔽在较高的光照水平下识别有用的视觉，但阴性掩蔽和PLR的辐照敏感性降低有限，并且两者的变化幅度低估了成像视觉的辐照敏感性降低。这些数据共同表明，在给定的疾病中，对光的两种反应可以以相反的方式受到影响，并且对于给定的对光反应，反应的变化并不能准确地代表病理的程度。然而，PLR的缺陷程度意味着即使是有限的视杆/视锥功能的挽救也可以通过增加PLR振幅来测量。此外，正掩蔽有可能通过恢复响应或将阈值转移到较低的辐照度来测量两种模型中的有效治疗。
Pre-clinical testing of retinal pathology and treatment efficacy depends on reliable and valid measures of retinal function. The electroretinogram (ERG) and tests of visual acuity are the ideal standard, but can be unmeasurable while useful vision remains. Non-image-forming responses to light such as the pupillary light reflex (PLR) are attractive surrogates. However, it is not clear how accurately such responses reflect changes in visual capability in specific disease models. The purpose of this study was to test whether measures of non-visual responses to light correlate with previously determined visual function in two photoreceptor degenerations. The sensitivity of masking behavior (light induced changes in running wheel activity) and the PLR were measured in 3-month-old wild-type mice (WT) with intact inner retinal circuitry, Pde6b-rd1/rd1 mice (rd1) with early and rapid loss of rods and cones, and Prph2-Rd2/Rd2 mice (Rd2) with a slower progressive loss of rods and cones. In rd1 mice, negative masking had increased sensitivity, positive masking was absent, and the sensitivity of the PLR was severely reduced. In Rd2 mice, positive masking identified useful vision at higher light levels, but there was a limited decrease in the irradiance sensitivity of negative masking and the PLR, and the amplitude of change for both underestimated the reduction in irradiance sensitivity of image-forming vision. Together these data show that in a given disease, two responses to light can be affected in opposite ways, and that for a given response to light, the change in the response does not accurately represent the degree of pathology. However, the extent of the deficit in the PLR means that even a limited rescue of rod/cone function might be measured by increased PLR amplitude. In addition, positive masking has the potential to measure effective treatment in both models by restoring responses or shifting thresholds to lower irradiances.
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影响因子：
12.4
作者：
Pang, JJ;Chang, B;Hauswirth, WW
通讯作者：
Hauswirth, WW
影响因子：
1.8
作者：
Prusky, GT;West, PWR;Douglas, RM
通讯作者：
Douglas, RM
影响因子：
3.4
作者：
Crippa, Sylvain, V;Domellof, Fatima Pedrosa;Kawasaki, Aki
通讯作者：
Kawasaki, Aki
影响因子：
8.8
作者：
Care RA;Anastassov IA;Kastner DB;Kuo YM;Della Santina L;Dunn FA
通讯作者：
Dunn FA
DOI：
10.1007/s10633-016-9535-0
发表时间：
2016-06
期刊：
Documenta ophthalmologica. Advances in ophthalmology
影响因子：
--
作者：
Collison FT;Park JC;Fishman GA;Stone EM;McAnany JJ
通讯作者：
McAnany JJ