{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:48:44Z","timestamp":1790884124140,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T00:00:00Z","timestamp":1654732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health and Medical Research Fund (HMRF) of Hong Kong Food and Health Bureau","award":["P0030128"],"award-info":[{"award-number":["P0030128"]}]},{"name":"Health and Medical Research Fund (HMRF) of Hong Kong Food and Health Bureau","award":["P0005240"],"award-info":[{"award-number":["P0005240"]}]},{"name":"Health and Medical Research Fund (HMRF) of Hong Kong Food and Health Bureau","award":["P0000347"],"award-info":[{"award-number":["P0000347"]}]},{"name":"Health and Medical Research Fund (HMRF) of Hong Kong Food and Health Bureau","award":["P0039595"],"award-info":[{"award-number":["P0039595"]}]},{"name":"Health and Medical Research Fund (HMRF) of Hong Kong Food and Health Bureau","award":["P0039545"],"award-info":[{"award-number":["P0039545"]}]},{"name":"General Research Fund (GRF) from the Hong Kong Research Grants Council","award":["P0030128"],"award-info":[{"award-number":["P0030128"]}]},{"name":"General Research Fund (GRF) from the Hong Kong Research Grants Council","award":["P0005240"],"award-info":[{"award-number":["P0005240"]}]},{"name":"General Research Fund (GRF) from the Hong Kong Research Grants Council","award":["P0000347"],"award-info":[{"award-number":["P0000347"]}]},{"name":"General Research Fund (GRF) from the Hong Kong Research Grants Council","award":["P0039595"],"award-info":[{"award-number":["P0039595"]}]},{"name":"General Research Fund (GRF) from the Hong Kong Research Grants Council","award":["P0039545"],"award-info":[{"award-number":["P0039545"]}]},{"name":"Project of Strategic Importance of The Hong Kong Polytechnic University","award":["P0030128"],"award-info":[{"award-number":["P0030128"]}]},{"name":"Project of Strategic Importance of The Hong Kong Polytechnic University","award":["P0005240"],"award-info":[{"award-number":["P0005240"]}]},{"name":"Project of Strategic Importance of The Hong Kong Polytechnic University","award":["P0000347"],"award-info":[{"award-number":["P0000347"]}]},{"name":"Project of Strategic Importance of The Hong Kong Polytechnic University","award":["P0039595"],"award-info":[{"award-number":["P0039595"]}]},{"name":"Project of Strategic Importance of The Hong Kong Polytechnic University","award":["P0039545"],"award-info":[{"award-number":["P0039545"]}]},{"name":"Research Centre for SHARP Vision (RCSV) of The Hong Kong Polytechnic University and The Hong Kong Special Administrative Region Government and InnoHK","award":["P0030128"],"award-info":[{"award-number":["P0030128"]}]},{"name":"Research Centre for SHARP Vision (RCSV) of The Hong Kong Polytechnic University and The Hong Kong Special Administrative Region Government and InnoHK","award":["P0005240"],"award-info":[{"award-number":["P0005240"]}]},{"name":"Research Centre for SHARP Vision (RCSV) of The Hong Kong Polytechnic University and The Hong Kong Special Administrative Region Government and InnoHK","award":["P0000347"],"award-info":[{"award-number":["P0000347"]}]},{"name":"Research Centre for SHARP Vision (RCSV) of The Hong Kong Polytechnic University and The Hong Kong Special Administrative Region Government and InnoHK","award":["P0039595"],"award-info":[{"award-number":["P0039595"]}]},{"name":"Research Centre for SHARP Vision (RCSV) of The Hong Kong Polytechnic University and The Hong Kong Special Administrative Region Government and InnoHK","award":["P0039545"],"award-info":[{"award-number":["P0039545"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Uveitis is a group of sight-threatening ocular inflammatory diseases, potentially leading to permanent vision loss in patients. However, it remains largely unknown how uveitis causes retinal malfunction and vision loss. Endotoxin-induced uveitis (EIU) in rodents is a good animal model to study uveitis and associated acute retinal inflammation. To understand the pathogenic mechanism of uveitis and screen potential targets for treatment, we analyzed the retinal proteomic profile of the EIU mouse model using a data-independent acquisition-based mass spectrometry (SWATH-MS). After systemic LPS administration, we observed activation of microglial cells accompanied with the elevation of pro-inflammatory mediators and visual function declines. In total, we observed 79 upregulated and 90 downregulated differentially expressed proteins (DEPs). Among the DEPs, we found that histone family members (histone H1, H2A, H2B) and blood proteins including haptoglobin (HP), hemopexin (HPX), and fibrinogen gamma chain (FGG) were dramatically increased in EIU groups relative to those in control groups. We identified phototransduction and synaptic vesicle cycle as the top two significant KEGG pathways. Moreover, canonical pathway analysis on DEPs using Ingenuity Pathway Analysis revealed top three most significant enriched pathways related to acute phase response signaling, synaptogenesis signaling, and eif2 signaling. We further confirmed upregulation of several DEPs associated with the acute phase response signaling including HP, HPX, and FGG in LPS-treated retinas by qPCR and Western blot. In summary, this study serves as the first report to detect retinal proteome changes in the EIU model. The study provides several potential candidates for exploring the mechanism and novel therapeutic targets for uveitis and other retinal inflammatory diseases.<\/jats:p>","DOI":"10.3390\/ijms23126464","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T02:25:33Z","timestamp":1654827933000},"page":"6464","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Retinal Proteomic Analysis in a Mouse Model of Endotoxin-Induced Uveitis Using Data-Independent Acquisition-Based Mass Spectrometry"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7525-2075","authenticated-orcid":false,"given":"Jing","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangmei","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2804-2424","authenticated-orcid":false,"given":"Daqian","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1938-8397","authenticated-orcid":false,"given":"Chi-Ho","family":"To","sequence":"additional","affiliation":[{"name":"School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China"},{"name":"Centre for Eye and Vision Research (CEVR), Hong Kong SAR, China"},{"name":"Research Centre for SHARP Vision (RCSV), The Hong Kong Polytechnic University, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3511-5620","authenticated-orcid":false,"given":"Thomas Chuen","family":"Lam","sequence":"additional","affiliation":[{"name":"School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China"},{"name":"Centre for Eye and Vision Research (CEVR), Hong Kong SAR, China"},{"name":"Research Centre for SHARP Vision (RCSV), The Hong Kong Polytechnic University, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China"},{"name":"Centre for Eye and Vision Research (CEVR), Hong Kong SAR, China"},{"name":"Research Centre for SHARP Vision (RCSV), The Hong Kong Polytechnic University, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1136\/bjo.80.9.844","article-title":"The possible impact of uveitis in blindness: A literature survey","volume":"80","author":"Rothova","year":"1996","journal-title":"Br. J. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"705","DOI":"10.5301\/ejo.5000278","article-title":"Review on the worldwide epidemiology of uveitis","volume":"23","author":"Miserocchi","year":"2013","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.survophthal.2016.12.008","article-title":"Viral posterior uveitis","volume":"62","author":"Lee","year":"2017","journal-title":"Surv. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1111\/ceo.13517","article-title":"Epidemiology of uveitis in urban Australia","volume":"47","author":"Hart","year":"2019","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Shirahama, S., Kaburaki, T., Nakahara, H., Tanaka, R., Takamoto, M., Fujino, Y., Kawashima, H., and Aihara, M. (2018). Epidemiology of uveitis (2013\u20132015) and changes in the patterns of uveitis (2004\u20132015) in the central Tokyo area: A retrospective study. BMC Ophthalmol., 18.","DOI":"10.1186\/s12886-018-0871-6"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1097\/ICU.0000000000000810","article-title":"Update on ophthalmic manifestations of systemic lupus erythematosus: Pathogenesis and precision medicine","volume":"32","author":"Lee","year":"2021","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1097\/ICU.0000000000000809","article-title":"Vogt-Koyanagi-Harada disease","volume":"32","author":"Joye","year":"2021","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1136\/bjo.76.3.137","article-title":"Uveitis and systemic disease","volume":"76","author":"Rothova","year":"1992","journal-title":"Br. J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/978-1-62703-481-4_18","article-title":"Endotoxin-induced uveitis in rodents","volume":"1031","author":"Yadav","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/286611a0","article-title":"Endotoxin-induced uveitis in rats as a model for human disease","volume":"286","author":"Rosenbaum","year":"1980","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1146\/annurev-bioeng-061008-124934","article-title":"Proteomics by mass spectrometry: Approaches, advances, and applications","volume":"11","author":"Yates","year":"2009","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bian, J., Sze, Y.H., Tse, D.Y., To, C.H., McFadden, S.A., Lam, C.S., Li, K.K., and Lam, T.C. (2021). SWATH Based Quantitative Proteomics Reveals Significant Lipid Metabolism in Early Myopic Guinea Pig Retina. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094721"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"814814","DOI":"10.3389\/fphar.2022.814814","article-title":"Alteration of EIF2 Signaling, Glycolysis, and Dopamine Secretion in Form-Deprived Myopia in Response to 1% Atropine Treatment: Evidence From Interactive iTRAQ-MS and SWATH-MS Proteomics Using a Guinea Pig Model","volume":"13","author":"Zhu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"610428","DOI":"10.3389\/fimmu.2020.610428","article-title":"Protein Biomarkers in Uveitis","volume":"11","author":"Bansal","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.1002\/pmic.200500779","article-title":"Identification of crystallin family proteins in vitreous body in rat endotoxin-induced uveitis: Involvement of crystallin truncation in uveitis pathogenesis","volume":"6","author":"Bahk","year":"2006","journal-title":"Proteomics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1002\/pmic.201400270","article-title":"SWATH enables precise label-free quantification on proteome scale","volume":"15","author":"Huang","year":"2015","journal-title":"Proteomics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1002\/glia.20467","article-title":"Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration","volume":"55","author":"Qin","year":"2007","journal-title":"Glia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cyto.2008.01.006","article-title":"LPS\/TLR4 signal transduction pathway","volume":"42","author":"Lu","year":"2008","journal-title":"Cytokine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9989","DOI":"10.1073\/pnas.1820387116","article-title":"Retinal microglia initiate neuroinflammation in ocular autoimmunity","volume":"116","author":"Okunuki","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Li, R., Liang, Y., and Lin, B. (2022). Accumulation of systematic TPM1 mediates inflammation and neuronal remodeling by phosphorylating PKA and regulating the FABP5\/NF-kappaB signaling pathway in the retina of aged mice. Aging Cell, e13566.","DOI":"10.1111\/acel.13566"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"441","DOI":"10.2217\/fmb.15.151","article-title":"Histones as mediators of host defense, inflammation and thrombosis","volume":"11","author":"Hoeksema","year":"2016","journal-title":"Future Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2356","DOI":"10.4049\/jimmunol.168.5.2356","article-title":"Endotoxin-neutralizing antimicrobial proteins of the human placenta","volume":"168","author":"Kim","year":"2002","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3929","DOI":"10.1021\/bi0268394","article-title":"Histones: A novel class of lipopolysaccharide-binding molecules","volume":"42","author":"Augusto","year":"2003","journal-title":"Biochemistry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.4049\/jimmunol.1203181","article-title":"Human CRP defends against the toxicity of circulating histones","volume":"191","author":"Abrams","year":"2013","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1006\/exer.1998.0494","article-title":"Expression of the protective proteins hemopexin and haptoglobin by cells of the neural retina","volume":"67","author":"Chen","year":"1998","journal-title":"Exp. Eye Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.2337\/dc12-2634","article-title":"Overexpression of hemopexin in the diabetic eye: A new pathogenic candidate for diabetic macular edema","volume":"36","author":"Hernandez","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"147507","DOI":"10.1016\/j.brainres.2021.147507","article-title":"Effect of hemopexin treatment on outcome after intracerebral hemorrhage in mice","volume":"1765","author":"Li","year":"2021","journal-title":"Brain Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12974-016-0490-1","article-title":"Deletion of the hemopexin or heme oxygenase-2 gene aggravates brain injury following stroma-free hemoglobin-induced intracerebral hemorrhage","volume":"13","author":"Ma","year":"2016","journal-title":"J. Neuroinflammation"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.expneurol.2019.01.011","article-title":"Temporal and age-dependent effects of haptoglobin deletion on intracerebral hemorrhage-induced brain damage and neurobehavioral outcomes","volume":"317","author":"Leclerc","year":"2019","journal-title":"Exp. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11814","DOI":"10.1073\/pnas.0704045104","article-title":"Fibrinogen inhibits neurite outgrowth via beta 3 integrin-mediated phosphorylation of the EGF receptor","volume":"104","author":"Schachtrup","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/j.neuron.2019.01.014","article-title":"Fibrinogen Induces Microglia-Mediated Spine Elimination and Cognitive Impairment in an Alzheimer\u2019s Disease Model","volume":"101","author":"Merlini","year":"2019","journal-title":"Neuron"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"147569","DOI":"10.1016\/j.brainres.2021.147569","article-title":"Accelerated accumulation of fibrinogen peptide chains with Abeta deposition in Alzheimer\u2019s disease (AD) mice and human AD brains","volume":"1767","author":"Bian","year":"2021","journal-title":"Brain Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1002\/elps.1150180333","article-title":"A comparison of selected mRNA and protein abundances in human liver","volume":"18","author":"Anderson","year":"1997","journal-title":"Electrophoresis"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.1016\/j.visres.2004.07.041","article-title":"Visual experience and maturation of retinal synaptic pathways","volume":"44","author":"Tian","year":"2004","journal-title":"Vision Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.arr.2014.01.003","article-title":"Communication breakdown: The impact of ageing on synapse structure","volume":"14","author":"Petralia","year":"2014","journal-title":"Ageing Res. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1007\/s11064-012-0708-2","article-title":"Neuroinflammation and synaptic loss","volume":"37","author":"Rao","year":"2012","journal-title":"Neurochem. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1523\/JNEUROSCI.2469-20.2020","article-title":"Traumatic Brain Injury Causes Chronic Cortical Inflammation and Neuronal Dysfunction Mediated by Microglia","volume":"41","author":"Witcher","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"28738","DOI":"10.1074\/jbc.M112.375915","article-title":"Eukaryotic initiation factor 2 (eIF2) signaling regulates proinflammatory cytokine expression and bacterial invasion","volume":"287","author":"Shrestha","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1002\/JLB.4A0219-050R","article-title":"Leukocyte transcriptional signatures dependent on LPS dosage in human endotoxemia","volume":"106","author":"Khan","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1097\/00001756-200212200-00011","article-title":"Phosphorylation of eukaryotic initiation factor-2alpha (eIF2alpha) is associated with neuronal degeneration in Alzheimer\u2019s disease","volume":"13","author":"Chang","year":"2002","journal-title":"Neuroreport"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"E782","DOI":"10.1002\/humu.21055","article-title":"Mutations in the GUCA1A gene involved in hereditary cone dystrophies impair calcium-mediated regulation of guanylate cyclase","volume":"30","author":"Kitiratschky","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3389\/fnmol.2014.00045","article-title":"Membrane guanylyl cyclase complexes shape the photoresponses of retinal rods and cones","volume":"7","author":"Wen","year":"2014","journal-title":"Front. Mol. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s10633-013-9420-z","article-title":"Disease progression in autosomal dominant cone-rod dystrophy caused by a novel mutation (D100G) in the GUCA1A gene","volume":"128","author":"Nong","year":"2014","journal-title":"Doc. Ophthalmol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1038\/gim.2016.217","article-title":"GUCA1A mutation causes maculopathy in a five-generation family with a wide spectrum of severity","volume":"19","author":"Chen","year":"2017","journal-title":"Genet. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e97919","DOI":"10.1172\/jci.insight.97919","article-title":"A specific phosphorylation regulates the protective role of alphaA-crystallin in diabetes","volume":"3","author":"Ruebsam","year":"2018","journal-title":"JCI Insight"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"ENEURO-0045","DOI":"10.1523\/ENEURO.0045-22.2022","article-title":"Evidence for Paracrine Protective Role of Exogenous alphaA-Crystallin in Retinal Ganglion Cells","volume":"9","author":"Nath","year":"2022","journal-title":"Eneuro"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5559","DOI":"10.1167\/iovs.08-2842","article-title":"Mitochondrial proteomics in experimental autoimmune uveitis oxidative stress","volume":"50","author":"Saraswathy","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8449","DOI":"10.1167\/iovs.15-17524","article-title":"Comparative Proteomic Analysis of Two Uveitis Models in Lewis Rats","volume":"56","author":"Pepple","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1167\/iovs.08-2493","article-title":"Neuroprotective effect of an antioxidant, lutein, during retinal inflammation","volume":"50","author":"Sasaki","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3534","DOI":"10.2174\/1381612824666180924141407","article-title":"Protective Role of Endogenous PACAP in Inflammation-induced Retinal Degeneration","volume":"24","author":"Vaczy","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"891","DOI":"10.2353\/ajpath.2009.081115","article-title":"Arginase activity mediates retinal inflammation in endotoxin-induced uveitis","volume":"175","author":"Zhang","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1186\/s12974-020-01993-0","article-title":"Cyclooxygenase-1 mediates neuroinflammation and neurotoxicity in a mouse model of retinitis pigmentosa","volume":"17","author":"Yang","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41597-021-00813-1","article-title":"High-pH reversed-phase fractionated neural retina proteome of normal growing C57BL\/6 mouse","volume":"8","author":"Sze","year":"2021","journal-title":"Sci. Data"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1038\/nprot.2013.092","article-title":"Large-scale gene function analysis with the PANTHER classification system","volume":"8","author":"Mi","year":"2013","journal-title":"Nat. Protoc."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","article-title":"Causal analysis approaches in Ingenuity Pathway Analysis","volume":"30","author":"Kramer","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"D543","DOI":"10.1093\/nar\/gkab1038","article-title":"The PRIDE database resources in 2022: A hub for mass spectrometry-based proteomics evidences","volume":"50","author":"Bai","year":"2022","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/12\/6464\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:27:17Z","timestamp":1760138837000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/12\/6464"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,9]]},"references-count":57,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["ijms23126464"],"URL":"https:\/\/doi.org\/10.3390\/ijms23126464","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,9]]}}}