John A. Moran Eye Center, University of Utah, 65 Mario Capecchi Drive, Salt Lake City, UT 84132, USA.
Polgenix, Inc., Department of Medical Devices, 5171 California Ave., Suite 150, Irvine, CA, USA 92617.
Neuroscience. 2019 Sep 15;416:100-108. doi: 10.1016/j.neuroscience.2019.07.047. Epub 2019 Aug 7.
Two-photon vision arises from the perception of pulsed infrared (IR) laser light as color corresponding to approximately half of the laser wavelength. The physical process responsible for two-photon vision in rods has been delineated and verified experimentally only recently. Here, we sought to determine whether IR light can also be perceived by mammalian cone photoreceptors via a similar activation mechanism. To investigate selectively mammalian cone signaling in mice, we used animals with disabled rod signal transduction. We found that, contrary to the expected progressive sensitivity decrease based on the one-photon cone visual pigment spectral template, the sensitivity of mouse cone photoreceptors decreases only up to 800 nm and then increases at 900 nm and 1000 nm. Similarly, in experiments with the parafoveal region of macaque retinas, we found that the spectral sensitivity of primate cones diverged above the predicted one-photon spectral sensitivity template beyond 800 nm. In both cases, efficient detection of IR light was dependent on minimizing the dispersion of the ultrashort light pulses, indicating a non-linear two-photon activation process. Together, our studies demonstrate that mammalian cones can be activated by near IR light by a nonlinear two-photon excitation. Our results pave the way for the creation of a two-photon IR-based ophthalmoscope for the simultaneous imaging and functional testing of human retinas as a novel tool for the diagnosis and treatment of a wide range of visual disorders.
双光子视觉是由于人眼将脉冲红外（IR）激光光感知为与激光波长的大约一半相对应的颜色而产生的。最近，人们才刚刚从物理过程的角度阐明并验证了 rods 中双光子视觉的作用机制。在这里，我们试图确定 IR 光是否也可以通过类似的激活机制被哺乳动物的 cone 光感受器感知。为了选择性地研究小鼠中的哺乳动物 cone 信号，我们使用了 rod 信号转导功能丧失的动物。我们发现，与基于单光子 cone 视觉色素光谱模板的预期渐进灵敏度降低相反，mouse cone 光感受器的灵敏度仅在 800nm 以下降低，然后在 900nm 和 1000nm 处增加。同样，在对猕猴视网膜周边区域的实验中，我们发现，在 800nm 以上，灵长类动物的 cone 光谱灵敏度偏离了预测的单光子光谱灵敏度模板。在这两种情况下，高效检测 IR 光都依赖于最大限度地减少超短光脉冲的色散，这表明存在非线性双光子激活过程。总之，我们的研究表明，哺乳动物的 cone 可以通过非线性双光子激发被近 IR 光激活。我们的研究结果为创建基于双光子 IR 的眼科显微镜铺平了道路，该显微镜可用于同时对人视网膜进行成像和功能测试，作为诊断和治疗各种视觉障碍的新型工具。
