Deepak K. Pattanaik , Vasudevan Lakshminarayanan , Nachieketa K Sharma , Amir Prasad Sahu
{"title":"Leading edge of the a-wave of the electroretinogram and sodium iodate-induced age-related macular degeneration: A model","authors":"Deepak K. Pattanaik , Vasudevan Lakshminarayanan , Nachieketa K Sharma , Amir Prasad Sahu","doi":"10.1016/j.jtbi.2024.111879","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Iron-induced oxidative stress was thought to be the reason why the <em>a</em>-wave amplitude of the electroretinogram (ERG) dropped when iron ions were present.</p><p>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 <em>a</em>-wave amplitude in mice with sodium iodate-induced age-related macular degeneration is explained.</p></div><div><h3>Methods</h3><p>The leading edge of the <em>a</em>-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 <em>a</em>-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.</p></div><div><h3>Results</h3><p>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 <em>a</em>-wave. The calcium influx, misaligned photoreceptors, and total photoreceptor loss all cause the amplitude of the <span><math><mi>a</mi></math></span>-wave to decrease, and at any time from the beginning of phototransduction cascade, the calcium influx causes the slope of the <em>a</em>-wave to increase.</p></div><div><h3>Conclusion</h3><p>The reduction in the <em>a</em>-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.</p></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"592 ","pages":"Article 111879"},"PeriodicalIF":1.9000,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Theoretical Biology","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0022519324001632","RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
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.
Methods
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.
Results
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 -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.
Conclusion
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.
期刊介绍：
The Journal of Theoretical Biology is the leading forum for theoretical perspectives that give insight into biological processes. It covers a very wide range of topics and is of interest to biologists in many areas of research, including:
• Brain and Neuroscience
• Cancer Growth and Treatment
• Cell Biology
• Developmental Biology
• Ecology
• Evolution
• Immunology,
• Infectious and non-infectious Diseases,
• Mathematical, Computational, Biophysical and Statistical Modeling
• Microbiology, Molecular Biology, and Biochemistry
• Networks and Complex Systems
• Physiology
• Pharmacodynamics
• Animal Behavior and Game Theory
Acceptable papers are those that bear significant importance on the biology per se being presented, and not on the mathematical analysis. Papers that include some data or experimental material bearing on theory will be considered, including those that contain comparative study, statistical data analysis, mathematical proof, computer simulations, experiments, field observations, or even philosophical arguments, which are all methods to support or reject theoretical ideas. However, there should be a concerted effort to make papers intelligible to biologists in the chosen field.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
