Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science University, Portland, Oregon, USA.
Invest Ophthalmol Vis Sci. 2012 Sep 14;53(10):6232-44. doi: 10.1167/iovs.12-9569.
To assess structural, functional, and visual behavioral relationships in mutant rhodopsin transgenic (Tg) rats and to determine whether early optokinetic tracking (OKT) visual experience, known to permanently elevate visual thresholds in normal rats, can enhance vision in rats with photoreceptor degeneration.
Eight lines of pigmented Tg rats and RCS rats were used in this study. OKT thresholds were tested at single ages (1, 2, 3, 4, and 6 months) in naïve groups of rats, or daily in groups that began at eye-opening (P15) or 10 days later (P25). Electroretinogram (ERG) response amplitudes were recorded after OKT testing, and outer nuclear layer (ONL) thickness measurements were then obtained.
OKT thresholds, when measured at a single time point in naïve Tg lines beginning at P30, did not decline until months after significant photoreceptor loss. Daily testing of Tg lines resulted mostly with OKT thresholds inversely related to photoreceptor degeneration, with rapid degenerations resulting in sustained OKT thresholds for long periods despite the rapid photoreceptor loss. Slower degenerations resulted in rapid decline of thresholds, long before the loss of most photoreceptors, which was even more pronounced when daily testing began at eye opening. This amplified loss of function was not a result of testing-induced damage to the rod or cone photoreceptors, as ERG amplitudes and ONL thicknesses were the same as untested controls.
The unexpected lack of correlation of OKT testing with photoreceptor degeneration in the Tg rats emphasizes the need in behavioral therapeutic studies for careful analysis of visual thresholds of experimental animals prior to therapeutic intervention.
评估突变视紫红质转基因（Tg）大鼠的结构、功能和视觉行为关系，并确定早期光运动跟踪（OKT）视觉经验是否可以增强感光细胞变性大鼠的视力，这种经验已知可永久性提高正常大鼠的视觉阈值。
本研究使用了 8 种色素 Tg 大鼠和 RCS 大鼠。在未经训练的大鼠组中，在单一年龄（1、2、3、4 和 6 个月）测试 OKT 阈值，或在从睁眼（P15）或 10 天后（P25）开始的组中每天测试 OKT 阈值。在 OKT 测试后记录视网膜电图（ERG）响应幅度，然后获得外核层（ONL）厚度测量值。
当在从 P30 开始的 P30 开始的 naïve Tg 线的单个时间点测量 OKT 阈值时，直到数月后发生明显的感光细胞丧失，才会下降。对 Tg 线进行每日测试，大多数情况下，OKT 阈值与感光细胞变性呈反比，快速变性导致 OKT 阈值持续很长时间，尽管感光细胞迅速丧失。较慢的变性导致阈值迅速下降，在大多数感光细胞丧失之前更为明显，而当每日测试从睁眼开始时则更为明显。这种放大的功能丧失不是由于测试对杆状或锥状光感受器的损伤所致，因为 ERG 幅度和 ONL 厚度与未经测试的对照相同。
Tg 大鼠中 OKT 测试与感光细胞变性之间出乎意料的缺乏相关性，强调了在行为治疗研究中，在进行治疗干预之前，需要仔细分析实验动物的视觉阈值。
