College of Nursing, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
Biophotonics Laboratory, Department of Computer and Electrical Engineering and Computer Science, Florida Atlantic University, Boca Ratan, FL, USA.
Sci Rep. 2020 Nov 23;10(1):20382. doi: 10.1038/s41598-020-77290-w.
Photobiomodulation (PBM) by far-red (FR) to near-infrared (NIR) light has been demonstrated to restore the function of damaged mitochondria, increase the production of cytoprotective factors and prevent cell death. Our laboratory has shown that FR PBM improves functional and structural outcomes in animal models of retinal injury and retinal degenerative disease. The current study tested the hypothesis that a brief course of NIR (830 nm) PBM would preserve mitochondrial metabolic state and attenuate photoreceptor loss in a model of retinitis pigmentosa, the P23H transgenic rat. P23H rat pups were treated with 830 nm light (180 s; 25 mW/cm; 4.5 J/cm) using a light-emitting diode array (Quantum Devices, Barneveld, WI) from postnatal day (p) 10 to p25. Sham-treated rats were restrained, but not treated with 830 nm light. Retinal metabolic state, function and morphology were assessed at p30 by measurement of mitochondrial redox (NADH/FAD) state by 3D optical cryo-imaging, electroretinography (ERG), spectral-domain optical coherence tomography (SD-OCT), and histomorphometry. PBM preserved retinal metabolic state, retinal function, and retinal morphology in PBM-treated animals compared to the sham-treated group. PBM protected against the disruption of the oxidation state of the mitochondrial respiratory chain observed in sham-treated animals. Scotopic ERG responses over a range of flash intensities were significantly greater in PBM-treated rats compared to sham controls. SD-OCT studies and histological assessment showed that PBM preserved the structural integrity of the retina. These findings demonstrate for the first time a direct effect of NIR PBM on retinal mitochondrial redox status in a well-established model of retinal disease. They show that chronic proteotoxic stress disrupts retinal bioenergetics resulting in mitochondrial dysfunction, and retinal degeneration and that therapies normalizing mitochondrial metabolism have considerable potential for the treatment of retinal degenerative disease.
迄今为止，远红光（FR）到近红外光（NIR）的光生物调节（PBM）已被证明可以恢复受损线粒体的功能，增加细胞保护因子的产生并防止细胞死亡。我们的实验室已经表明，FR PBM 可改善视网膜损伤和视网膜退行性疾病动物模型的功能和结构结果。本研究检验了以下假设：即短暂的 NIR（830nm）PBM 治疗可在色素性视网膜炎模型（P23H 转基因大鼠）中保持线粒体代谢状态并减轻光感受器损失。P23H 幼鼠从出生后第 10 天（p）到 p25 每天接受 830nm 光（180s；25mW/cm；4.5J/cm）治疗，使用发光二极管阵列（Quantum Devices，Barneveld，WI）。假处理大鼠被束缚，但不接受 830nm 光治疗。通过 3D 光学冷冻成像、视网膜电图（ERG）、光谱域光学相干断层扫描（SD-OCT）和组织形态计量学评估 p30 时的视网膜代谢状态、功能和形态。与假处理组相比，PBM 治疗组的视网膜代谢状态、视网膜功能和视网膜形态得到了保留。PBM 可防止假处理动物中线粒体呼吸链氧化状态的破坏。与假对照相比，PBM 处理大鼠在一系列闪光强度下的暗适应 ERG 反应明显更大。SD-OCT 研究和组织学评估表明，PBM 保留了视网膜的结构完整性。这些发现首次证明了 NIR PBM 对视网膜疾病模型中线粒体氧化还原状态的直接影响。它们表明，慢性蛋白毒性应激会破坏视网膜生物能学，导致线粒体功能障碍和视网膜变性，而使线粒体代谢正常化的治疗方法对治疗视网膜退行性疾病具有很大的潜力。
