{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:33:36Z","timestamp":1790746416341,"version":"4.1.0"},"reference-count":77,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T00:00:00Z","timestamp":1643414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R01EY024905"],"award-info":[{"award-number":["R01EY024905"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Advanced age is one of the leading risk factors for vision loss and eye disease. Photoreceptors are the primary sensory neurons of the eye. The extended photoreceptor cell lifespan, in addition to its high metabolic needs due to phototransduction, makes it critical for these neurons to continually respond to the stresses associated with aging by mounting an appropriate gene expression response. Here, we sought to untangle the more general neuronal age-dependent transcriptional signature of photoreceptors with that induced by light stress. To do this, we aged flies or exposed them to various durations of blue light, followed by photoreceptor nuclei-specific transcriptome profiling. Using this approach, we identified genes that are both common and uniquely regulated by aging and light induced stress. Whereas both age and blue light induce expression of DNA repair genes and a neuronal-specific signature of death, both conditions result in downregulation of phototransduction. Interestingly, blue light uniquely induced genes that directly counteract the overactivation of the phototransduction signaling cascade. Lastly, unique gene expression changes in aging photoreceptors included the downregulation of genes involved in membrane potential homeostasis and mitochondrial function, as well as the upregulation of immune response genes. We propose that light stress contributes to the aging transcriptome of photoreceptors, but that there are also other environmental or intrinsic factors involved in age-associated photoreceptor gene expression signatures.<\/jats:p>","DOI":"10.3390\/genes13020264","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T23:02:06Z","timestamp":1643497326000},"page":"264","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Aging and Light Stress Result in Overlapping and Unique Gene Expression Changes in Photoreceptors"],"prefix":"10.3390","volume":"13","author":[{"given":"Spencer E.","family":"Escobedo","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0746-2529","authenticated-orcid":false,"given":"Sarah C.","family":"Stanhope","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5933-9952","authenticated-orcid":false,"given":"Vikki M.","family":"Weake","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA"},{"name":"Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1093\/geronj\/11.3.298","article-title":"Aging: A Theory Based on Free Radical and Radiation Chemistry","volume":"11","author":"Harman","year":"1956","journal-title":"J. Gerontol."},{"key":"ref_2","unstructured":"(2020, November 13). The Hallmarks of Aging, Available online: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3836174\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/wcs.1167","article-title":"Aging and Vision: Changes in Function and Performance from Optics to Perception","volume":"3","author":"Andersen","year":"2012","journal-title":"Wiley Interdiscip. Rev. Cogn. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hall, H., Medina, P., Cooper, D.A., Escobedo, S.E., Rounds, J., Brennan, K.J., Vincent, C., Miura, P., Doerge, R., and Weake, V.M. (2017). Transcriptome Profiling of Aging Drosophila Photoreceptors Reveals Gene Expression Trends That Correlate with Visual Senescence. BMC Genom., 18.","DOI":"10.1186\/s12864-017-4304-3"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"E6620","DOI":"10.1073\/pnas.1613833113","article-title":"Genetic Architecture of Natural Variation in Visual Senescence in Drosophila","volume":"113","author":"Carbone","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"ORSF48","DOI":"10.1167\/iovs.13-12840","article-title":"Age-Related Changes and Diseases of the Ocular Surface and Cornea","volume":"54","author":"Gipson","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1007\/s00347-015-0031-9","article-title":"Gesunder Glask\u00f6rper und seine Alterung","volume":"112","author":"Spitzer","year":"2015","journal-title":"Ophthalmologe"},{"key":"ref_8","first-page":"3278","article-title":"Aging of the Human Photoreceptor Mosaic: Evidence for Selective Vulnerability of Rods in Central Retina","volume":"34","author":"Curcio","year":"1993","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/S1568-1637(02)00007-7","article-title":"Photoreceptor Degeneration and Dysfunction in Aging and Age-Related Maculopathy","volume":"1","author":"Jackson","year":"2002","journal-title":"Ageing Res. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1146\/annurev-vision-100419-114940","article-title":"Aging of the Retina: Molecular and Metabolic Turbulences and Potential Interventions","volume":"7","author":"Campello","year":"2021","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_11","first-page":"A17","article-title":"Age-Related Eye Diseases: An Emerging Challenge for Public Health Professionals","volume":"2","author":"Maylahn","year":"2005","journal-title":"Prev. Chronic. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"895147","DOI":"10.1155\/2013\/895147","article-title":"Smoking and Age-Related Macular Degeneration: Review and Update","volume":"2013","author":"Velilla","year":"2013","journal-title":"J. Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Capurso, C., Bellanti, F., Lo Buglio, A., and Vendemiale, G. (2019). The Mediterranean Diet Slows Down the Progression of Aging and Helps to Prevent the Onset of Frailty: A Narrative Review. Nutrients, 12.","DOI":"10.3390\/nu12010035"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"a015370","DOI":"10.1101\/cshperspect.a015370","article-title":"Natural and Sun-Induced Aging of Human Skin","volume":"5","author":"Fisher","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1146\/annurev.physiol.64.082701.102229","article-title":"G Proteins and Phototransduction","volume":"64","author":"Arshavsky","year":"2002","journal-title":"Annu. Rev. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/s00424-007-0251-1","article-title":"Phototransduction and Retinal Degeneration in Drosophila","volume":"454","author":"Wang","year":"2007","journal-title":"Pflug. Arch.-Eur. J. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3389\/neuro.03.002.2009","article-title":"Drosophila Photoreceptors and Signaling Mechanisms","volume":"3","author":"Katz","year":"2009","journal-title":"Front. Cell Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1126\/science.175.4029.1486","article-title":"A Visual Pigment with Two Physiologically Active Stable States","volume":"175","author":"Hillman","year":"1972","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0065-2806(08)60264-7","article-title":"Insect Visual Pigments","volume":"Volume 13","author":"Treherne","year":"1978","journal-title":"Advances in Insect Physiology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ohx.2017.07.001","article-title":"A Programmable Optical Stimulator for the Drosophila Eye","volume":"2","author":"Chen","year":"2017","journal-title":"HardwareX"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14696","DOI":"10.1523\/JNEUROSCI.2456-12.2012","article-title":"Compartmentalization and Ca2+ Buffering Are Essential for Prevention of Light-Induced Retinal Degeneration","volume":"32","author":"Weiss","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"14","DOI":"10.4161\/19336950.2014.981439","article-title":"A New Genetic Model for Calcium Induced Autophagy and ER-Stress in Drosophila Photoreceptor Cells","volume":"9","author":"Weiss","year":"2015","journal-title":"Channels"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1016\/j.cub.2005.08.064","article-title":"Arrestin1 Mediates Light-Dependent Rhodopsin Endocytosis and Cell Survival","volume":"15","author":"Satoh","year":"2005","journal-title":"Curr. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0896-6273(00)00092-1","article-title":"A Molecular Pathway for Light-Dependent Photoreceptor Apoptosis in Drosophila","volume":"28","author":"Kiselev","year":"2000","journal-title":"Neuron"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41514-019-0038-6","article-title":"Daily Blue-Light Exposure Shortens Lifespan and Causes Brain Neurodegeneration in Drosophila","volume":"5","author":"Nash","year":"2019","journal-title":"NPJ Aging Mech. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1016\/j.jmb.2017.06.019","article-title":"Transcriptional Signatures of Aging","volume":"429","author":"Stegeman","year":"2017","journal-title":"J. Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/s41588-019-0351-9","article-title":"Retinal Transcriptome and EQTL Analyses Identify Genes Associated with Age-Related Macular Degeneration","volume":"51","author":"Ratnapriya","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5743","DOI":"10.1038\/s41467-019-12917-9","article-title":"Single-Nuclei RNA-Seq on Human Retinal Tissue Provides Improved Transcriptome Profiling","volume":"10","author":"Liang","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Hall, H., Ma, J., Shekhar, S., Leon-Salas, W.D., and Weake, V.M. (2018). Blue Light Induces a Neuroprotective Gene Expression Program in Drosophila Photoreceptors. BMC Neurosci., 19.","DOI":"10.1186\/s12868-018-0443-y"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1017\/S0016672300029402","article-title":"Tissue Specific Effects of Ommochrome Pathway Mutations in Drosophila Melanogaster","volume":"57","author":"Tearle","year":"1991","journal-title":"Genet. Res."},{"key":"ref_31","first-page":"e51418","article-title":"Affinity-Based Isolation of Tagged Nuclei from Drosophila Tissues for Gene Expression Analysis","volume":"85","author":"Ma","year":"2014","journal-title":"JoVE (J. Vis. Exp.)"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1080\/19336934.2021.1915683","article-title":"Characterizing a Gene Expression Toolkit for Eye- and Photoreceptor-Specific Expression in Drosophila","volume":"15","author":"Escobedo","year":"2021","journal-title":"Fly"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"iyab079","DOI":"10.1093\/genetics\/iyab079","article-title":"In Vivo Tissue-Specific Chromatin Profiling in Drosophila Melanogaster Using GFP-Tagged Nuclei","volume":"218","author":"Bakhle","year":"2021","journal-title":"Genetics"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"(2021, September 15). Trimmomatic: A Flexible Trimmer for Illumina Sequence Data|Bioinformatics|Oxford Academic. Available online: https:\/\/academic.oup.com\/bioinformatics\/article\/30\/15\/2114\/2390096.","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-Based Genome Alignment and Genotyping with HISAT2 and HISAT-Genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"(2021, September 15). Sequence Alignment\/Map Format and SAMtools|Bioinformatics|Oxford Academic. Available online: https:\/\/academic.oup.com\/bioinformatics\/article\/25\/16\/2078\/204688.","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2014A Python Framework to Work with High-Throughput Sequencing Data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_38","unstructured":"(2021, September 15). Normalization of RNA-Seq Data Using Factor Analysis of Control Genes or Samples|Nature Biotechnology. Available online: https:\/\/www.nature.com\/articles\/nbt.2931."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"EdgeR: A Bioconductor Package for Differential Expression Analysis of Digital Gene Expression Data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_40","unstructured":"Kolde, R. (2021, October 03). Pheatmap: Pretty Heatmaps. Available online: https:\/\/CRAN.R-project.org\/package=pheatmap."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"ClusterProfiler: An R Package for Comparing Biological Themes among Gene Clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS J. Integr. Biol."},{"key":"ref_42","unstructured":"(2021, September 15). Clusterprofiler 4.0: A Universal Enrichment Tool for Interpreting Omics Data: The Innovation. Available online: https:\/\/www.cell.com\/the-innovation\/fulltext\/S2666-675800066-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2666675821000667%3Fshowall%3Dtrue."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"16923","DOI":"10.1038\/srep16923","article-title":"Efficient Test and Visualization of Multi-Set Intersections","volume":"5","author":"Wang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e12817","DOI":"10.1111\/acel.12817","article-title":"Proper Splicing Contributes to Visual Function in the Aging Drosophila Eye","volume":"17","author":"Stegeman","year":"2018","journal-title":"Aging Cell"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Juan Jauregui-Lozano, J., Hall, H., Stanhope, S.C., Bakhle, K., Marlin, M.M., and Weake, V.M. (2021). The Clock: Cycle Complex Is a Major Transcriptional Regulator of Drosophila Photoreceptors That Protects the Eye from Retinal Degeneration and Oxidative Stress. PLoS Genet.","DOI":"10.1101\/2021.09.27.461946"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41514-017-0019-6","article-title":"Cytochrome B5 Protects Photoreceptors from Light Stress-Induced Lipid Peroxidation and Retinal Degeneration","volume":"3","author":"Chen","year":"2017","journal-title":"NPJ Aging Mech. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"356","DOI":"10.4161\/fly.5.4.17809","article-title":"Molecular Genetics of Retinal Degeneration","volume":"5","author":"Shieh","year":"2011","journal-title":"Fly"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"732","DOI":"10.3389\/fnins.2017.00732","article-title":"Drosophila Melanogaster White Mutant W1118 Undergo Retinal Degeneration","volume":"11","author":"Ferreiro","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.3109\/02713688509003351","article-title":"Ultraviolet and Blue Light Induced Damage to the Drosophila Retina: Microspectrophotometry and Electrophysiology","volume":"4","author":"Stark","year":"1985","journal-title":"Curr. Eye Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"22853","DOI":"10.1039\/C9RA02567G","article-title":"Revealing a New Fluorescence Peak of the Enhanced Green Fluorescent Protein Using Three-Dimensional Fluorescence Spectroscopy","volume":"9","author":"Santos","year":"2019","journal-title":"RSC Adv."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e141","DOI":"10.1038\/lsa.2014.22","article-title":"Healthy, Natural, Efficient and Tunable Lighting: Four-Package White LEDs for Optimizing the Circadian Effect, Color Quality and Vision Performance","volume":"3","year":"2014","journal-title":"Light Sci. Appl."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/nmat4270","article-title":"A Revolution in Lighting","volume":"14","author":"Pust","year":"2015","journal-title":"Nat. Mater."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1038\/nmat4012","article-title":"Narrow-Band Red-Emitting Sr[LiAl\u2083N\u2084]:Eu2+ as a next-Generation LED-Phosphor Material","volume":"13","author":"Pust","year":"2014","journal-title":"Nat. Mater."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1038\/35048564","article-title":"Fluorescent Pigments in Corals Are Photoprotective","volume":"408","author":"Salih","year":"2000","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s00338-012-0994-9","article-title":"Screening by Coral Green Fluorescent Protein (GFP)-like Chromoproteins Supports a Role in Photoprotection of Zooxanthellae","volume":"32","author":"Smith","year":"2013","journal-title":"Coral. Reefs"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3389\/fmars.2018.00011","article-title":"Trade-Offs Associated with Photoprotective Green Fluorescent Protein Expression as Potential Drivers of Balancing Selection for Color Polymorphism in Reef Corals","volume":"5","author":"Quick","year":"2018","journal-title":"Front. Mar. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s11357-006-9010-z","article-title":"Extension of Mouse Lifespan by Overexpression of Catalase","volume":"28","author":"Schriner","year":"2006","journal-title":"Age"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.exger.2016.08.012","article-title":"Overexpression of Catalase in Mice Reduces Age-Related Oxidative Stress and Maintains Sperm Production","volume":"84","author":"Selvaratnam","year":"2016","journal-title":"Exp. Gerontol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e9613090","DOI":"10.1155\/2019\/9613090","article-title":"Role of Catalase in Oxidative Stress- and Age-Associated Degenerative Diseases","volume":"2019","author":"Nandi","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1080\/15384101.2015.1004937","article-title":"Neuronal Cell Cycle: The Neuron Itself and Its Circumstances","volume":"14","author":"Frade","year":"2015","journal-title":"Cell Cycle"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/0896-6273(94)90276-3","article-title":"Analysis of Cell Cycle-Related Gene Expression in Postmitotic Neurons: Selective Induction of Cyclin D1 during Programmed Cell Death","volume":"12","author":"Freeman","year":"1994","journal-title":"Neuron"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"9232","DOI":"10.1523\/JNEUROSCI.3347-04.2004","article-title":"Divide and Die: Cell Cycle Events as Triggers of Nerve Cell Death","volume":"24","author":"Herrup","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"767","DOI":"10.4161\/cc.3.6.901","article-title":"Why Do Neurons Enter the Cell Cycle?","volume":"3","author":"Kruman","year":"2004","journal-title":"Cell Cycle"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1474-9728.2005.00147.x","article-title":"Aging of the Innate Immune Response in Drosophila Melanogaster","volume":"4","author":"Zerofsky","year":"2005","journal-title":"Aging Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"160","DOI":"10.12688\/f1000research.13117.1","article-title":"The Interplay between Immunity and Aging in Drosophila","volume":"7","author":"Garschall","year":"2018","journal-title":"F1000Res"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.18632\/aging.101922","article-title":"Impaired Ribosome Biogenesis: Mechanisms and Relevance to Cancer and Aging","volume":"11","author":"Turi","year":"2019","journal-title":"Aging (Albany NY)"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"8799","DOI":"10.1523\/JNEUROSCI.19-20-08799.1999","article-title":"Modulation of the Light Response by CAMP InDrosophila Photoreceptors","volume":"19","author":"Chyb","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"10703","DOI":"10.1523\/JNEUROSCI.2061-10.2010","article-title":"Autophagy-Dependent Rhodopsin Degradation Prevents Retinal Degeneration in Drosophila","volume":"30","author":"Midorikawa","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"C1017","DOI":"10.1152\/ajpcell.00185.2011","article-title":"KCNQ5\/Kv7.5 Potassium Channel Expression and Subcellular Localization in Primate Retinal Pigment Epithelium and Neural Retina","volume":"301","author":"Zhang","year":"2011","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.3389\/fphys.2018.01661","article-title":"Emerging Roles of the Membrane Potential: Action beyond the Action Potential","volume":"9","author":"Stacey","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"757","DOI":"10.2147\/CIA.S158513","article-title":"Oxidative Stress, Aging, and Diseases","volume":"13","author":"Liguori","year":"2018","journal-title":"Clin. Interv. Aging"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.3389\/fphar.2018.01162","article-title":"Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases","volume":"9","author":"Tan","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.arr.2005.02.005","article-title":"The Effects of Stress and Aging on Glutathione Metabolism","volume":"4","author":"Maher","year":"2005","journal-title":"Ageing Res. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/0005-2760(76)90212-5","article-title":"Effect of Glutathione Peroxidase Activity on Lipid Peroxidation in Biological Membranes","volume":"431","author":"McCay","year":"1976","journal-title":"Biochim. Biophys. Acta (BBA)-Lipids Lipid. Metab."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/S0891-5849(99)00275-0","article-title":"Redox State of Glutathione in Human Plasma","volume":"28","author":"Jones","year":"2000","journal-title":"Free Radic. Biol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.3109\/00365521.2014.964757","article-title":"A Sensitive Method for the Analysis of Glutathione in Porcine Hepatocytes","volume":"49","author":"Goll","year":"2014","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"100127","DOI":"10.1016\/j.mcpro.2021.100127","article-title":"Quantitative Proteomic and Metabolomic Profiling Reveals Altered Mitochondrial Metabolism and Folate Biosynthesis Pathways in the Aging Drosophila Eye","volume":"20","author":"Hall","year":"2021","journal-title":"Mol. Cell Proteom."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/2\/264\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:10:46Z","timestamp":1760134246000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/2\/264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,29]]},"references-count":77,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["genes13020264"],"URL":"https:\/\/doi.org\/10.3390\/genes13020264","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,29]]}}}