Developing an Outcome Measure With High Luminance for Optogenetics Treatment of Severe Retinal Degenerations and for Gene Therapy of Cone Diseases.

Developing an Outcome Measure With High Luminance for Optogenetics Treatment of Severe Retinal Degenerations and for Gene Therapy of Cone Diseases.
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DOI:
10.1167/iovs.16-19586
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发表时间:
2016-06-01
影响因子:
4.4
通讯作者:
Nirenberg S
Nirenberg S
中科院分区:
医学2区
文献类型:
--
作者:
Cideciyan AV;Roman AJ;Jacobson SG;Yan B;Pascolini M;Charng J;Pajaro S;Nirenberg S

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在很大的亮度范围内呈现不同大小、颜色和图案的刺激物。暗箱MP1中使用的滤光棒被一个定制的滑入托盘取代,该托盘可以从由额外计算机驱动的外部投影仪引入光线。对MP1软件进行了修改,以向驱动投影仪的计算机提供视网膜跟踪信息。通过使用高速视频系统同时对系统输入和输出进行成像来评估视网膜跟踪性能。在暗视和明视范围内,使用消色差和色栅/背景组合来测量空间分辨率。通过改进可实现的视网膜照度范围高达6.8logPot-TD;然而,在目前的工作中,仅在人体受试者中测试了高于−4至+3logPot-Td的较低范围。光学放大率被优化,用于低视力测试,光栅的范围从4.5到0.2周期/度。在正常受试者中,通过选择合适的条件和波长,获得了棒驱动的空间分辨率、短波长敏感(S-)锥和长/中波长敏感(L/M-)锥。来自一名蓝色锥体单色症患者的数据被用来确认调解。改良的mp1可被开发为一种疗效指标,用于严重视网膜变性、视力低下和异常眼球运动的患者,如计划进行光遗传学治疗的患者,以及计划通过基因治疗改善L/M视锥功能高于视杆细胞和S视锥功能的视锥疾病患者。
To present stimuli with varied sizes, colors, and patterns over a large range of luminance. The filter bar used in scotopic MP1 was replaced with a custom slide-in tray that introduces light from an external projector driven by an additional computer. MP1 software was modified to provide retinal tracking information to the computer driving the projector. Retinal tracking performance was evaluated by imaging the system input and the output simultaneously with a high-speed video system. Spatial resolution was measured with achromatic and chromatic grating/background combinations over scotopic and photopic ranges. The range of retinal illuminance achievable by the modification was up to 6.8 log photopic Trolands (phot-Td); however, in the current work, only a lower range over −4 to +3 log phot-Td was tested in human subjects. Optical magnification was optimized for low-vision testing with gratings from 4.5 to 0.2 cyc/deg. In normal subjects, spatial resolution driven by rods, short wavelength-sensitive (S-) cones, and long/middle wavelength-sensitive (L/M-) cones was obtained by the choice of adapting conditions and wavelengths of grating and background. Data from a patient with blue cone monochromacy was used to confirm mediation. The modified MP1 can be developed into an outcome measure for treatments in patients with severe retinal degeneration, very low vision, and abnormal eye movements such as those for whom treatment with optogenetics is planned, as well as for patients with cone disorders such as blue cone monochromacy for whom treatment with gene therapy is planned to improve L/M-cone function above a normal complement of rod and S-cone function.