{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:50:51Z","timestamp":1786971051032,"version":"build-2736575974"},"reference-count":75,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["RC2788872"],"award-info":[{"award-number":["RC2788872"]}]},{"name":"5xMille 2016 to Fondazione Bietti and Fondazione Roma (Italy)","award":["RC2788872"],"award-info":[{"award-number":["RC2788872"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Background: Epiretinal membrane (ERM) and proliferative diabetic retinopathy (PDR) belong to the group of vitreoretinal diseases, characterized by impairments at both the retina and the vitreous. The non-diabetic and diabetic forms of ERM (no-dERM and dERM) as well as the PDR are caused by microvascular disorder, which frequently occurs in association with inflammation and oxidative stress. To better characterize no-dERM, dERM, and PDR at the biomolecular level, we compared the expression of inflammatory, oxidative, lipidic peroxidation products, and complement receptors. Methods: Twenty-seven ocular fluids from patients who underwent phaco-vitrectomy were categorized as no-dERM (9, 4M\/5F; 70.4 \u00b1 6.4), dERM (6, 3M\/3F; 73.2 \u00b1 4.9), and PDR (6, 5M\/1F; 63.7 \u00b1 7.4). Six cataracts (CTR; 3M\/3F; 77.7 \u00b1 9.0) were collected for internal control of aqueous cells. Results: In aqueous cells, p65NFkB, iNOS, Nox1\/Nox4, and Nrf2 were significantly upregulated, and Keap1 was downregulated in dERM compared with PDR and no-dERM. In aqueous cells, a significant upregulation for C3aR1mRNA, C5aR1mRNA, and CFHmRNA were observed in dERM. In vitreous, C3a, C5b9, and MDA levels were significantly increased in dERM compared with PDR and no-dERM. Conclusions: Inflammatory and ROS products, as well as C3aR1\/C5aR1 and soluble MDA, appear of great interest, as their expression in aqueous and vitreous might have potential prognostic and therapeutic values.<\/jats:p>","DOI":"10.3390\/antiox14070841","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T11:58:07Z","timestamp":1751975887000},"page":"841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Oxidative Stress and Complement Activation in Aqueous Cells and Vitreous from Patient with Vitreoretinal Diseases: Comparison Between Diabetic ERM and PDR"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1158-0659","authenticated-orcid":false,"given":"Lucia","family":"Dinice","sequence":"first","affiliation":[{"name":"Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Science, IRCCS\u2014Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4099-0123","authenticated-orcid":false,"given":"Pamela","family":"Cosimi","sequence":"additional","affiliation":[{"name":"Surgical Retina Research Unit, IRCCS\u2014Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8777-197X","authenticated-orcid":false,"given":"Graziana","family":"Esposito","sequence":"additional","affiliation":[{"name":"Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Science, IRCCS\u2014Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5444-4377","authenticated-orcid":false,"given":"Fabio","family":"Scarinci","sequence":"additional","affiliation":[{"name":"Surgical Retina Research Unit, IRCCS\u2014Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Cacciamani","sequence":"additional","affiliation":[{"name":"Surgical Retina Research Unit, IRCCS\u2014Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1401-8020","authenticated-orcid":false,"given":"Concetta","family":"Cafiero","sequence":"additional","affiliation":[{"name":"Anatomic Pathology Unit, Fabrizio Spaziani Hospital, 03100 Frosinone, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Placentino","sequence":"additional","affiliation":[{"name":"Surgical Retina Research Unit, IRCCS\u2014Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Ripandelli","sequence":"additional","affiliation":[{"name":"Surgical Retina Research Unit, IRCCS\u2014Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9375-6071","authenticated-orcid":false,"given":"Alessandra","family":"Micera","sequence":"additional","affiliation":[{"name":"Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Science, IRCCS\u2014Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1159\/000434692","article-title":"Routes for Drug Delivery: Sustained-Release Devices","volume":"55","author":"Yun","year":"2016","journal-title":"Dev. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"O\u017c\u00f3g, M.K., Nowak-W\u0105s, M., and Rokicki, W. (2023). Pathophysiology and clinical aspects of epiretinal membrane\u2014Review. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1121270"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Vishwakarma, S., Gupta, R.K., Jakati, S., Tyagi, M., Pappuru, R.R., Reddig, K., Hendricks, G., Volkert, M.R., Khanna, H., and Chhablani, J. (2020). Molecular Assessment of Epiretinal Mem-brane: Activated Microglia, Oxidative Stress and Inflammation. Antioxidants, 9.","DOI":"10.3390\/antiox9080654"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.sjopt.2018.05.002","article-title":"Role of oxidative stress, inflammation, hypoxia and angiogenesis in the development of diabetic retinopathy","volume":"32","year":"2018","journal-title":"Saudi J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"100733","DOI":"10.1016\/j.xops.2025.100733","article-title":"Epiretinal Membrane Is Associated with Diabetic Retinopathy Severity and Cumulative Anti-VEGF Injections","volume":"5","author":"Kakihara","year":"2025","journal-title":"Ophthalmol. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"43603","DOI":"10.1155\/2007\/43603","article-title":"Oxidative stress and diabetic retinopathy","volume":"2007","author":"Kowluru","year":"2007","journal-title":"Exp. Diabetes Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.survophthal.2015.06.001","article-title":"Implication of oxidative stress in progression of diabetic retinopathy","volume":"61","author":"Behl","year":"2016","journal-title":"Surv. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/ceo.12506","article-title":"Nitric oxide and oxidative stress is associated with severity of diabetic retinopathy and retinal structural alterations","volume":"43","author":"Sharma","year":"2015","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3095","DOI":"10.1167\/iovs.14-16194","article-title":"Catalase therapy corrects oxidative stress-induced pathophysiology in incipient diabetic retinopathy","volume":"56","author":"Giordano","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Shin, E.S., Huang, Q., Gurel, Z., Sorenson, C.M., and Sheibani, N. (2014). High glucose alters retinal astrocytes phenotype through increased production of inflammatory cytokines and oxidative stress. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0103148"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.preteyeres.2017.03.002","article-title":"The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD","volume":"60","author":"Datta","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Huang, W., Li, G., Qiu, J., Gonzalez, P., and Challa, P. (2013). Protective effects of resveratrol in experimental retinal detachment. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075735"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1161\/CIRCRESAHA.110.223545","article-title":"Oxidative stress and diabetic complications","volume":"107","author":"Giacco","year":"2010","journal-title":"Circ. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"689","DOI":"10.2337\/db19-1009","article-title":"Retinopathy in a diet-induced type 2 diabetic rat model and role of epigenetic modifications","volume":"69","author":"Kowluru","year":"2020","journal-title":"Diabetes"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1167\/iovs.61.6.4","article-title":"Inhibiting NF-kappaB signaling activation reduces retinal neovascularization by promoting a polarization shift in macrophages","volume":"61","author":"Sui","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/cr.2010.178","article-title":"Crosstalk of reactive oxygen species and NF-kB signaling","volume":"21","author":"Morgan","year":"2011","journal-title":"Cell Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7350","DOI":"10.1074\/jbc.RA120.013093","article-title":"The stress response protein REDD1 promotes diabetes-induced oxidative stress in the retina by Keap1-independent Nrf2 degradation","volume":"295","author":"Miller","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3941","DOI":"10.1167\/iovs.13-11598","article-title":"Transcription factor Nrf2-mediated antioxidant defense system in the development of diabetic retinopathy","volume":"54","author":"Zhong","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/414813a","article-title":"Biochemistry and molecular cell biology of diabetic complications","volume":"414","author":"Brownlee","year":"2001","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"291","DOI":"10.2337\/db19-0514","article-title":"Understanding metabolic memory: A tale of two studies","volume":"69","author":"Miller","year":"2020","journal-title":"Diabetes"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1002\/jcp.29180","article-title":"Targeting epigenetic modifications as a potential therapeutic option for diabetic retinopathy","volume":"235","author":"Kumari","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41581-019-0135-6","article-title":"Epigenetics and epigenomics in diabetic kidney disease and metabolic memory","volume":"15","author":"Kato","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_23","first-page":"E3002","article-title":"Epigenomic profiling reveals an association between persistence of DNA methylation and metabolic memory in the DCCT\/EDIC type 1 diabetes cohort","volume":"113","author":"Chen","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s00418-004-0676-y","article-title":"Oxygen free radicals and redox biology of organells","volume":"122","author":"Moldovan","year":"2004","journal-title":"Histochem. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s40942-022-00390-4","article-title":"Do different lipid components accelerate the pathogenesis and severity of Diabetic Retinopathy?","volume":"8","author":"Mondal","year":"2022","journal-title":"Int. J. Retin. Vitr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1097\/CM9.0000000000002620","article-title":"Malondialdehyde levels in diabetic retinopathy patients: A systematic review and meta-analysis","volume":"136","author":"Jiang","year":"2023","journal-title":"Meta-Anal. Chin. Med. J."},{"key":"ref_27","first-page":"4184","article-title":"Comparative study on MDA, SOD and HBA1C Levels in patients of type 2 diabetes mellitus with retinopathy and without retinopathy","volume":"7","author":"Verma","year":"2016","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1007\/s13340-020-00450-w","article-title":"Evaluation of some oxidative markers in diabetes and diabetic retinopathy","volume":"12","author":"Shawki","year":"2021","journal-title":"Diabetol. Int."},{"key":"ref_29","first-page":"1298","article-title":"Lipid peroxidation and total antioxidant capacity in vitreous, aqueous humor, and blood samples from patients with diabetic retinopathy","volume":"17","author":"Mancino","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1097\/IAE.0000000000002288","article-title":"Increased complement levels in human vitreous aspirates of proliferative diabetic retinopathy and retinal detachment eyes","volume":"39","author":"Manoharan","year":"2019","journal-title":"Retina"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5071","DOI":"10.1167\/iovs.10-5289","article-title":"Oxidative stress and the regulation of complement activation in human glaucoma","volume":"51","author":"Tezel","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Shahulhameed, S., Vishwakarma, S., Chhablani, J., Tyagi, M., Pappuru, R.R., Jakati, S., Chakrabarti, S., and Kaur, I. (2020). A Systematic Investigation on Complement Pathway Activation in Diabetic Retinopathy. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00154"},{"key":"ref_33","first-page":"1856","article-title":"New insight into the role of the complement in the most common types of retinopathy-current literature review","volume":"11","author":"Chrzanowska","year":"2018","journal-title":"Int. J. Ophthalmol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"103757","DOI":"10.1016\/j.drudis.2023.103757","article-title":"Therapeutic targeting of the complement system in ocular disease","volume":"28","author":"Rathi","year":"2023","journal-title":"Drug Discov. Today"},{"key":"ref_35","first-page":"655","article-title":"Identification and localization of major soluble vitreous proteins in human ocular tissue","volume":"137","author":"Wu","year":"2004","journal-title":"Am. J. Ophthalmol."},{"key":"ref_36","first-page":"575","article-title":"The complement system and diabetic retinopathy","volume":"69","author":"Jiang","year":"2024","journal-title":"Surv. Ophthalmol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"E36","DOI":"10.1093\/nar\/30.9.e36","article-title":"Relative Expression Software Tool (REST\u00a9) for group wise comparison and statistical analysis of relative expression results in real-time PCR","volume":"30","author":"Pfaffl","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1097\/00005344-199710000-00019","article-title":"Activation of nuclear factor-kappaB in cultured endothelial cells by increased glucose concentration: Prevention by calphostin C","volume":"30","author":"Pieper","year":"1997","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"855","DOI":"10.2337\/diabetes.48.4.855","article-title":"Hyperglycemia-induced activation of nuclear transcription factor kappaB in vascular smooth muscle cells","volume":"48","author":"Yerneni","year":"1999","journal-title":"Diabetes"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-kB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.2337\/db07-1520","article-title":"Hyperglycemia-induced reactive oxygen species toxicity to endothelial cells is dependent on paracrine mediators","volume":"57","author":"Busik","year":"2008","journal-title":"Diabetes"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/sj.eye.6700642","article-title":"Inducible nitric oxide synthase and vascular endothelial growth factor are colocalized in the retinas of human subjects with diabetes","volume":"18","author":"Meersschaert","year":"2004","journal-title":"Eye"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1007\/s00125-007-0734-9","article-title":"Critical role of inducible nitric oxide synthase in degeneration of retinal capillaries in mice with streptozotocin-induced diabetes","volume":"50","author":"Zheng","year":"2007","journal-title":"Diabetologia"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1002\/glia.21068","article-title":"Inhibition of inducible nitric oxide synthase reverses the loss of functional hyperemia in diabetic retinopathy","volume":"58","author":"Mishra","year":"2010","journal-title":"Glia"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1189\/jlb.1206735","article-title":"Role of NF-kappaB in transcriptional regulation of the phagocyte NADPH oxidase by tumor necrosis factor-alpha","volume":"82","author":"Gauss","year":"2007","journal-title":"J. Leukoc. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5257","DOI":"10.1167\/iovs.07-0112","article-title":"Inducible nitric oxide synthase isoform is a key mediator of leukostasis and blood-retinal barrier breakdown in diabetic retinopathy","volume":"48","author":"Leal","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9216791","DOI":"10.1155\/2018\/9216791","article-title":"Intravitreal Bevacizumab Injection Attenuates Diabetic Retinopathy in Adult Rats with Experimentally Induced Diabetes in the Early Stage","volume":"2018","author":"Lv","year":"2018","journal-title":"J. Diabetes Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1089\/ars.2013.5814","article-title":"Evolution of NADPH oxidase inhibitors: Selectivity and mechanisms for target engagement","volume":"23","author":"Radermacher","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1253\/circj.CJ-11-0388","article-title":"Pathophysiological roles of NADPH oxidase\/nox family proteins in the vascular system. Review and perspective","volume":"75","author":"Ago","year":"2011","journal-title":"Circ. J."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kang, Q., and Yang, C. (2020). Oxidative stress and diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications. Redox Biol., 37.","DOI":"10.1016\/j.redox.2020.101799"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.7150\/ijbs.25996","article-title":"The Nrf 2 signaling in retinal ganglion cells under oxidative stress in ocular neurodegenerative diseases","volume":"14","author":"Liu","year":"2018","journal-title":"Int. J. Biol. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"122386","DOI":"10.1016\/j.lfs.2023.122386","article-title":"The role of Keap1-Nrf2 signaling pathway during the progress and therapy of diabetic retinopathy","volume":"338","author":"Chen","year":"2024","journal-title":"Life Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1007\/s00406-017-0848-0","article-title":"Keap1-Nrf2 signaling pathway confers resilience versus susceptibility to inescapable electric stress","volume":"268","author":"Zhang","year":"2018","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4826724","DOI":"10.1155\/2017\/4826724","article-title":"The Nrf2\/Keap1\/ARE pathway and oxidative stress as a therapeutic target in type II diabetes mellitus","volume":"2017","author":"David","year":"2017","journal-title":"J. Diabetes Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1089\/ars.2017.7358","article-title":"An overview of the advantages of KEAP1-NRF2 system activation during inflammatory disease treatment","volume":"29","author":"Suzuki","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.biopha.2016.11.089","article-title":"Hesperetin protects against H2O2-triggered oxidative damage via upregulation of the Keap1-Nrf2\/HO-1 signal pathway in ARPE-19 cells","volume":"88","author":"Zhu","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/978-3-319-17121-0_13","article-title":"Interrelation Between Oxidative Stress and Complement Activation in Models of Age-Related Macular Degeneration","volume":"854","author":"Kuhn","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/nri.2016.63","article-title":"Innate sensing of oxidation-specific epitopes in health and disease","volume":"16","author":"Binder","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Armento, A., Honisch, S., Panagiotakopoulou, V., Sonntag, I., Jacob, A., Bolz, S., Kilger, E., Deleidi, M., Clark, S., and Ueffing, M. (2020). Loss of Complement Factor H impairs antioxidant capacity and energy metabolism of human RPE cells. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-67292-z"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"100936","DOI":"10.1016\/j.preteyeres.2020.100936","article-title":"Targeting complement components C3 and C5 for the retina: Key concepts and lingering questions","volume":"83","author":"Kim","year":"2021","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3901","DOI":"10.1016\/j.molimm.2007.06.145","article-title":"The role of complement system in ocular diseases including uveitis and macular degeneration","volume":"44","author":"Jha","year":"2007","journal-title":"Mol. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1016\/j.ajpath.2018.06.018","article-title":"Complement 7 is up regulated in human early diabetic kidney disease","volume":"188","author":"Sircar","year":"2018","journal-title":"Am. J. Pathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1177\/1120672119857896","article-title":"Systemic activation of the complement system in patients with advanced age related macular degeneration","volume":"30","author":"Lynch","year":"2020","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1146\/annurev-immunol-032713-120154","article-title":"Complement and its receptors: New insights into human disease","volume":"32","author":"Holers","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/nri2620","article-title":"Complement regulators and inhibitory proteins","volume":"9","author":"Zipfel","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ejphar.2016.03.001","article-title":"Targeting the complement system for the management of retinal inflammatory and degenerative diseases","volume":"787","author":"Xu","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1167\/iovs.61.11.39","article-title":"Complement Activation in the Vitreous of Patients With Proliferative Diabetic Retinopathy","volume":"61","author":"Mandava","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1167\/tvst.12.11.9","article-title":"Correlation of Aqueous, Vitreous, and Serum Protein Levels in Patients With Retinal Diseases","volume":"12","author":"Wilson","year":"2023","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1189\/jlb.3RI0615-239R","article-title":"Parainflammation, chronic inflammation, and agerelated macular degeneration","volume":"98","author":"Chen","year":"2015","journal-title":"J. Leukoc. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Haydinger, C.D., Oliver, G.F., Ashander, L.M., and Smith, J.R. (2023). Oxidative Stress and Its Regulation in Diabetic Retinopathy. Antioxidants, 12.","DOI":"10.3390\/antiox12081649"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1196\/annals.1332.007","article-title":"Inflammation and the degenerative diseases of aging","volume":"1035","author":"McGeer","year":"2004","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"B\u00f6hm, E.W., Buonfiglio, F., Voigt, A.M., Bachmann, P., Safi, T., Pfeiffer, N., and Gericke, A. (2023). Oxidative stress in the eye and its role in the pathophysiology of ocular diseases. Redox Biol., 68.","DOI":"10.1016\/j.redox.2023.102967"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"101156","DOI":"10.1016\/j.apmt.2021.101156","article-title":"Targeting nanocomposites with anti-oxidative\/inflammatory\/angiogenic activities for synergistically alleviating macular degeneration","volume":"24","author":"Luo","year":"2021","journal-title":"Appl. Mater. Today"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Shastri, D.H., Silva, A.C., and Almeida, H. (2023). Ocular Delivery of Therapeutic Proteins: A Review. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010205"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Vora, L.K., Gholap, A.D., Jetha, K., Thakur, R.R.S., Solanki, H.K., and Chavda, V.P. (2023). Artificial Intelligence in Pharmaceutical Technology and Drug Delivery Design. 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