{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T01:28:05Z","timestamp":1793237285753,"version":"4.5.0"},"reference-count":82,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Combat Casualty Care Research Program at the United States Army Medical Research and Development Command","award":["C0210037"],"award-info":[{"award-number":["C0210037"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurology International"],"abstract":"<jats:p>Background\/Objectives: Blast-induced traumatic ocular injuries (bTOI) pose a significant risk to military and civilian populations, often leading to visual impairment or blindness. Retina, the innermost layer of ocular tissue consisting of photoreceptor and glial cells, is highly susceptible to blast injuries. Despite its prevalence, the molecular mechanisms underlying retinal damage following bTOI remain poorly understood, hindering the development of targeted therapies. Melatonin, a neuroprotective indoleamine with antioxidant, anti-inflammatory, and circadian regulatory properties, is synthesized in the retina and plays a crucial role in retinal health. Similarly, retina-specific genes, such as Rhodopsin, Melanopsin, and RPE65, are essential for photoreceptor function, visual signaling, and the visual cycle. However, their responses to blast exposure have not been thoroughly investigated. Methods: In this study, we utilized a ferret model of bTOI to evaluate the temporal expression of melatonin-synthesizing enzymes, such as tryptophan hydroxylase 1 and 2 (TPH1 and TPH2), Aralkylamine N-acetyltransferase (AANAT), and Acetylserotonin-O-methyltransferase (ASMT), and retina-specific genes (Rhodopsin, Melanopsin) and retinal pigment epithelium-specific 65 kDa protein (RPE65) at 4 h, 24 h, 7 days, and 28 days post-blast. Ferrets were exposed to tightly coupled blast overpressure waves using an advanced blast simulator, and retinal tissues were collected for quantitative polymerase chain reaction (qPCR) analysis. Results: The results revealed dynamic and multiphasic transcriptional responses. TPH1 and TPH2 exhibited significant upregulation at 24 h, followed by downregulation at 28 days, indicating blast-induced dysregulation of tryptophan metabolism, including melatonin synthesis. Similarly, AANAT and ASMT showed acute downregulation post-blast, with late-phase disruptions. Rhodopsin expression increased at 24 h but declined at 28 days, while Melanopsin and RPE65 demonstrated early upregulation followed by downregulation, reflecting potential disruptions in circadian regulation and the visual cycle. Conclusions: These findings highlight the complex regulatory mechanisms underlying retinal responses to bTOI, involving neuroinflammation, oxidative stress, and disruptions in melatonin synthesis and photoreceptor cell functions. The results emphasize the therapeutic potential of melatonin in mitigating retinal damage and preserving visual function.<\/jats:p>","DOI":"10.3390\/neurolint17030042","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T07:49:57Z","timestamp":1742197797000},"page":"42","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dysregulation of Retinal Melatonin Biosynthetic Pathway and Differential Expression of Retina-Specific Genes Following Blast-Induced Ocular Injury in Ferrets"],"prefix":"10.3390","volume":"17","author":[{"given":"Chetan","family":"Pundkar","sequence":"first","affiliation":[{"name":"Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5760-9437","authenticated-orcid":false,"given":"Rex Jeya Rajkumar Samdavid","family":"Thanapaul","sequence":"additional","affiliation":[{"name":"Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"},{"name":"National Research Council (NRC) Research Associateship Programs, National Academies of Sciences, Engineering, and Medicine, Washington, DC 20001, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4739-648X","authenticated-orcid":false,"given":"Manoj","family":"Govindarajulu","sequence":"additional","affiliation":[{"name":"Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaurav","family":"Phuyal","sequence":"additional","affiliation":[{"name":"Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8988-4628","authenticated-orcid":false,"given":"Joseph B.","family":"Long","sequence":"additional","affiliation":[{"name":"Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peethambaran","family":"Arun","sequence":"additional","affiliation":[{"name":"Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"key":"ref_1","unstructured":"National Academies of Sciences, Engineering, and Medicine, Health and Medicine Division, Board on Population Health and Public Health Practice, Committee on Public Health Approaches to Reduce Vision Impairment and Promote Eye Health, Welp, A., Woodbury, R.B., McCoy, M.A., and Teutsch, S.M. (2016). The Impact of Vision Loss. Making Eye Health a Population Health Imperative: Vision for Tomorrow, National Academies Press (US)."},{"key":"ref_2","first-page":"283","article-title":"Altered Expression of Aquaporin 1 and Aquaporin 5 in the Cornea after Primary Blast Exposure","volume":"25","author":"Choi","year":"2019","journal-title":"Mol. Vis."},{"key":"ref_3","first-page":"3","article-title":"Explosive Eye Injuries: Characteristics, Traumatic Mechanisms, and Prognostic Factors for Poor Visual Outcomes","volume":"10","author":"Zhang","year":"2023","journal-title":"Mil. Med. Res."},{"key":"ref_4","first-page":"42","article-title":"Traumatic Brain Injury and Sight Loss in Military and Veteran Populations\u2014A Review","volume":"8","author":"Hussain","year":"2021","journal-title":"Mil. Med. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3451","DOI":"10.1038\/s41433-020-01359-z","article-title":"Incidence of Ocular Blast Injuries in Modern Conflict","volume":"35","author":"McMaster","year":"2021","journal-title":"Eye"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2916","DOI":"10.1093\/milmed\/usac226","article-title":"Ocular Trauma and Traumatic Brain Injury on the Battlefield: A Systematic Review After 20 Years of Fighting the Global War on Terror","volume":"188","author":"Lee","year":"2023","journal-title":"Mil. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.dt.2024.03.006","article-title":"Blast Injury Risks to Humans within a Military Trench","volume":"40","author":"Edri","year":"2024","journal-title":"Def. Technol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1038\/eye.2011.212","article-title":"Ocular Injuries from Improvised Explosive Devices","volume":"25","author":"Erdurman","year":"2011","journal-title":"Eye"},{"key":"ref_9","unstructured":"(2025, January 16). Brain Injury and Vision Loss from Blast Trauma. Available online: https:\/\/www.aao.org\/eyenet\/article\/brain-injury-vision-loss-from-blast-trauma."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1210\/er.2018-00084","article-title":"do Melatonin as a Hormone: New Physiological and Clinical Insights","volume":"39","author":"Amaral","year":"2018","journal-title":"Endocr. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"107253","DOI":"10.1016\/j.phrs.2024.107253","article-title":"Melatonin: Unveiling the Functions and Implications in Ocular Health","volume":"205","author":"Zhang","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1007\/s00018-014-1579-2","article-title":"Extrapineal Melatonin: Sources, Regulation, and Potential Functions","volume":"71","author":"Escames","year":"2014","journal-title":"Cell Mol. Life Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"434","DOI":"10.2174\/1570159X14666161228122115","article-title":"Melatonin: Pharmacology, Functions and Therapeutic Benefits","volume":"15","author":"Tordjman","year":"2017","journal-title":"Curr. Neuropharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s12640-012-9337-4","article-title":"Melatonin Antioxidative Defense: Therapeutical Implications for Aging and Neurodegenerative Processes","volume":"23","author":"BaHammam","year":"2013","journal-title":"Neurotox. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yu, H., Wang, Q., Wu, W., Zeng, W., and Feng, Y. (2021). Therapeutic Effects of Melatonin on Ocular Diseases: Knowledge Map and Perspective. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.721869"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"La Morgia, C., Carelli, V., and Carbonelli, M. (2018). Melanopsin Retinal Ganglion Cells and Pupil: Clinical Implications for Neuro-Ophthalmology. Front. Neurol., 9.","DOI":"10.3389\/fneur.2018.01047"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"101013","DOI":"10.1016\/j.preteyeres.2021.101013","article-title":"Retinal Pigment Epithelium 65 kDa Protein (RPE65): An Update","volume":"88","author":"Kiser","year":"2022","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s11154-009-9120-x","article-title":"The Role of Retinal Photoreceptors in the Regulation of Circadian Rhythms","volume":"10","author":"Paul","year":"2009","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"137364","DOI":"10.1016\/j.neulet.2023.137364","article-title":"Upregulation of Multiple Toll-like Receptors in Ferret Brain after Blast Exposure: Potential Targets for Treatment","volume":"810","author":"Govindarajulu","year":"2023","journal-title":"Neurosci. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/9780470942390.mo110129","article-title":"Exploration of the Visual System: Part 1: Dissection of the Mouse Eye for RNA, Protein, and Histological Analyses","volume":"1","author":"Escher","year":"2011","journal-title":"Curr. Protoc. Mouse Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1007\/s00429-021-02322-8","article-title":"Distribution of Two Isoforms of Tryptophan Hydroxylase in the Brain of Rainbow Trout (Oncorhynchus Mykiss). An in Situ Hybridization Study","volume":"226","author":"Chivite","year":"2021","journal-title":"Brain Struct. Funct."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s00441-003-0822-1","article-title":"Localization of Aa-Nat mRNA in the Rat Retina by Fluorescence in Situ Hybridization and Laser Capture Microdissection","volume":"315","author":"Liu","year":"2004","journal-title":"Cell Tissue Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1002\/ajmg.b.32023","article-title":"Advances in Tryptophan Hydroxylase-2 Gene Expression Regulation: New Insights into Serotonin\u2013Stress Interaction and Clinical Implications","volume":"159B","author":"Chen","year":"2012","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/j.bcp.2013.02.018","article-title":"Tryptophan Hydroxylase-2: An Emerging Therapeutic Target for Stress Disorders","volume":"85","author":"Chen","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"DeMar, J., Sharrow, K., Hill, M., Berman, J., Oliver, T., and Long, J. (2016). Effects of Primary Blast Overpressure on Retina and Optic Tract in Rats. Front. Neurol., 7.","DOI":"10.3389\/fneur.2016.00059"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1167\/iovs.12-11522","article-title":"Retinal Ganglion Cell Damage in an Experimental Rodent Model of Blast-Mediated Traumatic Brain Injury","volume":"54","author":"Mohan","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"108102","DOI":"10.1016\/j.exer.2020.108102","article-title":"Assessment of Necroptosis in the Retina in a Repeated Primary Ocular Blast Injury Mouse Model","volume":"197","author":"Thomas","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"34","DOI":"10.7205\/MILMED-D-13-00504","article-title":"Pathophysiology of Blast-Induced Ocular Trauma With Apoptosis in the Retina and Optic Nerve","volume":"179","author":"Wang","year":"2014","journal-title":"Mil. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8330","DOI":"10.1167\/iovs.14-15468","article-title":"Early Detection of Subclinical Visual Damage after Blast-Mediated TBI Enables Prevention of Chronic Visual Deficit by Treatment with P7C3-S243","volume":"55","author":"Dutca","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4159","DOI":"10.1167\/iovs.19-27565","article-title":"Blast Preconditioning Protects Retinal Ganglion Cells and Reveals Targets for Prevention of Neurodegeneration Following Blast-Mediated Traumatic Brian Injury","volume":"60","author":"Harper","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e03374","DOI":"10.1016\/j.heliyon.2020.e03374","article-title":"Identification of Chronic Brain Protein Changes and Protein Targets of Serum Auto-Antibodies after Blast-Mediated Traumatic Brain Injury","volume":"6","author":"Harper","year":"2020","journal-title":"Heliyon"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1089\/neu.2017.5394","article-title":"Long-Term Functional and Structural Consequences of Primary Blast Overpressure to the Eye","volume":"35","author":"Allen","year":"2018","journal-title":"J. Neurotrauma"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1186\/s12974-014-0192-5","article-title":"Exacerbation of Blast-Induced Ocular Trauma by an Immune Response","volume":"11","author":"Rex","year":"2014","journal-title":"J. Neuroinflam."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4853","DOI":"10.1167\/iovs.14-14353","article-title":"Molecular Changes and Vision Loss in a Mouse Model of Closed-Globe Blast Trauma","volume":"55","author":"Rex","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Bricker-Anthony, C., and Rex, T.S. (2015). Neurodegeneration and Vision Loss after Mild Blunt Trauma in the C57Bl\/6 and DBA\/2J Mouse. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131921"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1080\/02713683.2019.1567791","article-title":"Blast Exposure Induces Ocular Functional Changes with Increasing Blast Over-Pressures in a Rat Model","volume":"44","author":"Zhu","year":"2019","journal-title":"Curr. Eye Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e12951","DOI":"10.1111\/jpi.12951","article-title":"Melatonin in the Mammalian Retina: Synthesis, Mechanisms of Action and Neuroprotection","volume":"76","author":"Hicks","year":"2024","journal-title":"J. Pineal Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.mce.2009.04.010","article-title":"The Melatonin-Producing System Is Fully Functional in Retinal Pigment Epithelium (ARPE-19)","volume":"307","author":"Sweatman","year":"2009","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/B978-0-444-64125-0.00012-8","article-title":"Chapter 12\u2014Tryptophan Hydroxylase and Serotonin Synthesis Regulation","volume":"Volume 31","author":"Cunningham","year":"2020","journal-title":"Handbook of Behavioral Neuroscience"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0169-328X(98)00219-8","article-title":"Circadian Expression of Tryptophan Hydroxylase mRNA in the Chicken Retina1","volume":"61","author":"Chong","year":"1998","journal-title":"Mol. Brain Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1046\/j.1471-4159.1994.62062420.x","article-title":"Tryptophan Hydroxylase Expression Is Regulated by a Circadian Clock in Xenopus Laevis Retina","volume":"62","author":"Green","year":"1994","journal-title":"J. Neurochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1089\/neu.2014.3669","article-title":"Neurotransmitter Systems in a Mild Blast Traumatic Brain Injury Model: Catecholamines and Serotonin","volume":"32","author":"Kawa","year":"2015","journal-title":"J. Neurotrauma"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kawa, L., Kamnaksh, A., Long, J.B., Arborelius, U.P., H\u00f6kfelt, T., Agoston, D.V., and Risling, M. (2018). A Comparative Study of Two Blast-Induced Traumatic Brain Injury Models: Changes in Monoamine and Galanin Systems Following Single and Repeated Exposure. Front. Neurol., 9.","DOI":"10.3389\/fneur.2018.00479"},{"key":"ref_44","unstructured":"Kawa, L. (2017). Experimental, Mild Blast-Induced Traumatic Brain Injury: Focus on the Monoamine and Galanin Systems. [Ph.D. Thesis, Karolinska Institutet]."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Govindarajulu, M., Patel, M.Y., Wilder, D.M., Long, J.B., and Arun, P. (2022). Blast Exposure Dysregulates Nighttime Melatonin Synthesis and Signaling in the Pineal Gland: A Potential Mechanism of Blast-Induced Sleep Disruptions. Brain Sci., 12.","DOI":"10.3390\/brainsci12101340"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.neulet.2006.01.019","article-title":"Hypotensive but Not Normotensive Haemorrhage Increases Tryptophan Hydroxylase-2 mRNA in Caudal Midline Medulla","volume":"398","author":"Brown","year":"2006","journal-title":"Neurosci. Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1196\/annals.1410.074","article-title":"Serotonergic Changes Produced by Repeated Exposure to Forced Swimming: Correlation with Behavior","volume":"1148","author":"Shishkina","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Boehme, N.A., Hedberg-Buenz, A., Tatro, N., Bielecki, M., Castonguay, W.C., Scheetz, T.E., Anderson, M.G., and Dutca, L.M. (2021). Axonopathy Precedes Cell Death in Ocular Damage Mediated by Blast Exposure. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-90412-2"},{"key":"ref_49","first-page":"4138-F0375","article-title":"Alterations of Retinal Pathophysiology Following Repeated Blast Injury Resulting from Reproduced Open-Field Blast Environment","volume":"63","author":"Ha","year":"2022","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Pomianowski, K., Gozdowska, M., Burzy\u0144ski, A., Kalamarz-Kubiak, H., Soko\u0142owska, E., Kijewska, A., and Kulczykowska, E. (2020). A Study of Aanat and Asmt Expression in the Three-Spined Stickleback Eye and Skin: Not Only \u201con the Way to Melatonin\u201d. Comp. Biochem. Physiol. Part A Mol. Integr. Physiol., 241.","DOI":"10.1016\/j.cbpa.2019.110635"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1080\/07420520500482066","article-title":"Regulation of Arylalkylamine N-Acetyltransferase (AANAT) in the Retina","volume":"23","author":"Tosini","year":"2006","journal-title":"Chronobiol. Int."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1089\/neu.2014.3640","article-title":"Neuronal DNA Methylation Profiling of Blast-Related Traumatic Brain Injury","volume":"32","author":"Haghighi","year":"2015","journal-title":"J. Neurotrauma"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1523\/JNEUROSCI.1685-18.2018","article-title":"Activation of 5-HT1A Receptors Promotes Retinal Ganglion Cell Function by Inhibiting the cAMP-PKA Pathway to Modulate Presynaptic GABA Release in Chronic Glaucoma","volume":"39","author":"Zhou","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Zhou, X., Li, G., Zhang, S., and Wu, J. (2019). 5-HT1A Receptor Agonist Promotes Retinal Ganglion Cell Function by Inhibiting OFF-Type Presynaptic Glutamatergic Activity in a Chronic Glaucoma Model. Front. Cell. Neurosci., 13.","DOI":"10.3389\/fncel.2019.00167"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Liang, H., Liu, N., Wang, R., Zhang, Y., Chen, J., Dai, Z., Yang, Y., Wu, G., and Wu, Z. (2020). N-Acetyl Serotonin Alleviates Oxidative Damage by Activating Nuclear Factor Erythroid 2-Related Factor 2 Signaling in Porcine Enterocytes. Antioxidants, 9.","DOI":"10.3390\/antiox9040303"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Biswal, M.R., Paulson, R.J., Vichare, R., and Lewin, A.S. (2023). Buspirone Enhances Cell Survival and Preserves Structural Integrity during Oxidative Injury to the Retinal Pigment Epithelium. Antioxidants, 12.","DOI":"10.3390\/antiox12122129"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.pneurobio.2016.03.007","article-title":"How Serotonin Receptors Regulate Morphogenic Signalling in Neurons","volume":"151","author":"Wirth","year":"2017","journal-title":"Prog. Neurobiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.biochi.2018.11.006","article-title":"Serotonin in Retina","volume":"161","author":"Masson","year":"2019","journal-title":"Biochimie"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1001\/archopht.1997.01100150222012","article-title":"Serotonin-Induced Constriction of Ocular Arteries in Atherosclerotic Monkeys. Implications for Ischemic Disorders of the Retina and Optic Nerve Head","volume":"115","author":"Hayreh","year":"1997","journal-title":"Arch. Ophthalmol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0167-5273(87)90008-8","article-title":"Serotonin and the Vascular Wall","volume":"14","author":"Vanhoutte","year":"1987","journal-title":"Int. J. Cardiol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Maddaloni, G., Barsotti, N., Migliarini, S., Giordano, M., Nazzi, S., Picchi, M., Errico, F., Usiello, A., and Pasqualetti, M. (2024). Impact of Serotonin Deficiency on Circadian Dopaminergic Rhythms. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25126475"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0306-4522(98)00733-7","article-title":"Electrical Stimulation of the Median or Dorsal Raphe Nuclei Reduces Light-Induced FOS Protein in the Suprachiasmatic Nucleus and Causes Circadian Activity Rhythm Phase Shifts","volume":"92","author":"Morin","year":"1999","journal-title":"Neuroscience"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Ramkisoensing, A., and Meijer, J.H. (2015). Synchronization of Biological Clock Neurons by Light and Peripheral Feedback Systems Promotes Circadian Rhythms and Health. Front. Neurol., 6.","DOI":"10.3389\/fneur.2015.00128"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1152\/physrev.2001.81.4.1659","article-title":"Rhodopsin: Structural Basis of Molecular Physiology","volume":"81","author":"Menon","year":"2001","journal-title":"Physiol. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S0968-0004(01)01799-6","article-title":"Activation of Rhodopsin: New Insights from Structural and Biochemical Studies","volume":"26","author":"Okada","year":"2001","journal-title":"Trends Biochem. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4196","DOI":"10.1167\/iovs.19-26966","article-title":"Visual Contrast Sensitivity Correlates to the Retinal Degeneration in Rhodopsin Knockout Mice","volume":"60","author":"Xiao","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5233","DOI":"10.1073\/pnas.0408892102","article-title":"In Vivo Dynamics of Retinal Injury and Repair in the Rhodopsin Mutant Dog Model of Human Retinitis Pigmentosa","volume":"102","author":"Cideciyan","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Lenahan, C., Sanghavi, R., Huang, L., and Zhang, J.H. (2020). Rhodopsin: A Potential Biomarker for Neurodegenerative Diseases. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.00326"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.tins.2013.08.003","article-title":"Rhodopsin Homeostasis and Retinal Degeneration: Lessons from the Fly","volume":"36","author":"Xiong","year":"2013","journal-title":"Trends Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Di Pierdomenico, J., Garc\u00eda-Ayuso, D., Pinilla, I., Cuenca, N., Vidal-Sanz, M., Agudo-Barriuso, M., and Villegas-P\u00e9rez, M.P. (2017). Early Events in Retinal Degeneration Caused by Rhodopsin Mutation or Pigment Epithelium Malfunction: Differences and Similarities. Front. Neuroanat., 11.","DOI":"10.3389\/fnana.2017.00014"},{"key":"ref_71","first-page":"A76","article-title":"Changes In Retinal Opsins Reflect Neurological Abnormalities in Multiple Models of Traumatic Brain Injury","volume":"38","author":"Parsons","year":"2021","journal-title":"J. Neurotrauma"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.exer.2017.05.010","article-title":"Light-Induced Retinal Degeneration Causes a Transient Downregulation of Melanopsin in the Rat Retina","volume":"161","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4309","DOI":"10.1167\/iovs.15-16963","article-title":"Transient Downregulation of Melanopsin Expression After Retrograde Tracing or Optic Nerve Injury in Adult Rats","volume":"56","author":"Madeira","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"113063","DOI":"10.1016\/j.expneurol.2019.113063","article-title":"Amelioration of Visual Deficits and Visual System Pathology after Mild TBI via the Cannabinoid Type-2 Receptor Inverse Agonism of Raloxifene","volume":"322","author":"Honig","year":"2019","journal-title":"Exp. Neurol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.neuroscience.2014.11.002","article-title":"The Injury Resistant Ability of Melanopsin-Expressing Intrinsically Photosensitive Retinal Ganglion Cells","volume":"284","author":"Cui","year":"2015","journal-title":"Neuroscience"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Xue, Y., Shen, S.Q., Corbo, J.C., and Kefalov, V.J. (2015). Circadian and Light-Driven Regulation of Rod Dark Adaptation. Sci. Rep., 5.","DOI":"10.1038\/srep17616"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1080\/13816810802626399","article-title":"RPE65: Role in the Visual Cycle, Human Retinal Disease, and Gene Therapy","volume":"30","author":"Cai","year":"2009","journal-title":"Ophthalmic Genet."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0002-9394(62)90401-4","article-title":"The Pigment Epithelium of the Human Eye","volume":"53","author":"Kaczurowski","year":"1962","journal-title":"Am. J. Ophthalmol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1196\/annals.1356.029","article-title":"Effects of Melatonin in Age-Related Macular Degeneration","volume":"1057","author":"Yi","year":"2005","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Fujishiro, T., Kawasaki, H., Aihara, M., Saeki, T., Ymagishi, R., Atarashi, T., Mayama, C., and Araie, M. (2014). Establishment of an Experimental Ferret Ocular Hypertension Model for the Analysis of Central Visual Pathway Damage. Sci. Rep., 4.","DOI":"10.1038\/srep06501"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.exer.2009.03.013","article-title":"Morphological Changes in the Visual Pathway Induced by Experimental Glaucoma in Japanese Monkeys","volume":"89","author":"Ito","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.exer.2005.08.001","article-title":"Morphometric Evaluation of Changes with Time in Optic Disc Structure and Thickness of Retinal Nerve Fibre Layer in Chronic Ocular Hypertensive Monkeys","volume":"82","author":"Shimazawa","year":"2006","journal-title":"Exp. Eye Res."}],"container-title":["Neurology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2035-8377\/17\/3\/42\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:54:48Z","timestamp":1760028888000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2035-8377\/17\/3\/42"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,17]]},"references-count":82,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["neurolint17030042"],"URL":"https:\/\/doi.org\/10.3390\/neurolint17030042","relation":{},"ISSN":["2035-8377"],"issn-type":[{"value":"2035-8377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,17]]}}}