背景:铁诱导的氧化应激被认为是当铁离子存在时视网膜电图(ERG)的a波振幅下降的原因。假设在铁离子存在下产生活性氧(ROS),这导致感光体的超极化减少。众所周知,在年龄相关性黄斑变性(AMD)中,碘酸钠可以诱导氧化应激,凋亡,和视网膜损伤,模拟临床AMD的影响。这里,解释了碘酸钠诱导的年龄相关性黄斑变性小鼠a波振幅的降低。
方法:a波的前缘被分成由锥体和杆形成的电压。同样的氧化应激模型也适用于此,因为碘酸钠以类似于铁离子引起的方式产生ROS,例外的是,当计算光响应时,视网膜被视为具有各种电阻的电路。此外,碘酸钠也会导致细胞凋亡,因此,在AMD细胞凋亡的初始阶段,可能会导致视锥细胞(而不是视杆)错位。包括视锥细胞和视杆细胞凋亡和缩短的影响,我们已经使用了一个因子来表示活的全部视锥和杆的分数。为了包括锥体不对准对a波振幅减小的影响,我们已经使用Stiles-Crawford函数来计算在角度θ未对准的感光体中发生的光异构化的数量。将结果与实验数据进行比较。
结果:在碘酸钠治疗的眼睛中,产生的ROS可以吸引感光体中的钙离子,这增加了钙的流入。在锥体的情况下,在光传导过程中包含未对准角有助于确定电压和电压的斜率与时间图。活性光感受器的比例越小,a波的振幅越小。钙的流入,错位的光感受器,和感光体的总损失都会导致a波的振幅降低,从光传导级联开始的任何时候,钙流入导致a波的斜率增加。
结论:碘酸钠处理的小鼠眼睛中a波振幅的降低归因于视锥和视杆的氧化应激和视锥错位,最终导致AMD的细胞凋亡和视力丧失。
Iron-induced oxidative stress was thought to be the reason why the a-wave amplitude of the electroretinogram (ERG) dropped when iron ions were present. It is assumed that reactive oxygen species (ROS) are generated in the presence of iron ions, and this leads to a decrease in hyperpolarization of the photoreceptor. It is known that in age-related macular degeneration (AMD), sodium iodate can induce oxidative stress, apoptosis, and retinal damage, which mimic the effects of clinical AMD. Here, the reduction of the a-wave amplitude in mice with sodium iodate-induced age-related macular degeneration is explained.
The leading edge of the a-wave is divided into voltages developed by cones and rods. The same oxidative stress model is applied here since sodium iodate causes the creation of ROS in a manner similar to that caused by iron ions, with the exception that the retina is treated as a circuit of various resistances when computing the photoresponse. Moreover, sodium iodate also leads to apoptosis and, hence, may cause misalignment in cones (not in rods) during the initial stage of apoptosis in AMD. To include the effects of apoptosis and shortening in cones and rods, we have used a factor representing the fraction of total cones and rods that are alive. To include the effect of misalignment of cones on the reduction of the a-wave amplitude, we have used the Stiles-Crawford function to calculate the number of photoisomerizations occurring in a photoreceptor misaligned at an angle θ. The results are compared with experimental data.
In sodium iodate-treated eyes, the ROS produced can attract calcium ions in the photoreceptor, which increases the calcium influx. In the case of the cones, the inclusion of the misalignment angle in the phototransduction process helps in determining the voltage and slope of the voltage vs. time graph.The smaller the fraction of active photoreceptors, the smaller the amplitude of the a-wave. The calcium influx, misaligned photoreceptors, and total photoreceptor loss all cause the amplitude of the a-wave to decrease, and at any time from the beginning of phototransduction cascade, the calcium influx causes the slope of the a-wave to increase.
The reduction in the a-wave amplitude in the eyes of sodium iodate-treated mice is attributed to oxidative stress in both cones and rods and cone misalignment, which ultimately lead to apoptosis and vision loss in AMD.