{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:18:22Z","timestamp":1790936302529,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T00:00:00Z","timestamp":1723852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Retinopathy of prematurity (ROP) has a dual-phase disease pathology; in phase 1, hyperoxia-induced vaso-obliteration occurs in the retinal vasculature due to increased oxidative stress (OS) and inflammation, followed by phase 2, where hypoxia increases the overproduction of growth factors, inducing retinal neovascularization. Toll-like receptor 2 and -4 (TLR2 and TLR4) overactivation, hyper-inflammation, macrophages, and neutrophil infiltration contribute to the developing ROP. AVR-121 and AVR-123 are novel classes of small-molecule dual inhibitors of TLR2\/4 tested in a human leukemia monocytic cell line (THP-1) and cord-blood-derived mononuclear cells (CBMCs). Both compounds inhibited TLR2\/4 signaling-related inflammatory cytokines in THP-1 cells and inhibited VEGF-induced neovascularization in human retinal endothelial cells (HRECs), which are hallmarks of ROP. In an oxygen-induced retinopathy (OIR) murine model, the intraperitoneal injection of AVR-123 in the hyperoxia phase (P7\u2013P12) or a nanosuspension eyedrop of AVR-123 in the hypoxic phase (P12\u2013P17) significantly reduced vaso-obliteration, angiogenesis, and inflammatory cytokine profiles while not inhibiting the necessary growth factor VEGF in the juvenile mouse eyes. The results are consistent with our hypothesis that targeting the dual TLR2\/4 pathway will reduce inflammation, angiogenesis, and vaso-obliteration in vitro and in vivo and reduce cytotoxic immune cells. AVR-123 has the potential to be developed as a therapy for ROP.<\/jats:p>","DOI":"10.3390\/cells13161371","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T03:43:28Z","timestamp":1724039008000},"page":"1371","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Novel Small Molecules with Anti-Inflammatory and Anti-Angiogenic Activity in a Mouse Model of Oxygen-Induced Retinopathy"],"prefix":"10.3390","volume":"13","author":[{"given":"Adam S.","family":"Dayoub","sequence":"first","affiliation":[{"name":"AyuVis Research Inc., Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eesha","family":"Acharya","sequence":"additional","affiliation":[{"name":"AyuVis Research Inc., Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnan","family":"Dibas","sequence":"additional","affiliation":[{"name":"The North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harlan P.","family":"Jones","sequence":"additional","affiliation":[{"name":"The North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suchismita","family":"Acharya","sequence":"additional","affiliation":[{"name":"AyuVis Research Inc., Fort Worth, TX 76107, USA"},{"name":"The North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.survophthal.2018.04.002","article-title":"Retinopathy of prematurity: A review of risk factors and their clinical significance","volume":"63","author":"Kim","year":"2018","journal-title":"Surv. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wu, P.Y., Fu, Y.K., Lien, R.I., Chiang, M.C., Lee, C.C., Chen, H.C., Hsueh, Y.J., Chen, K.J., Wang, N.K., and Liu, L. (2023). Systemic Cytokines in Retinopathy of Prematurity. J. Pers. Med., 13.","DOI":"10.3390\/jpm13020291"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/pr.2013.205","article-title":"Preterm-associated visual impairment and estimates of retinopathy of prematurity at regional and global levels for 2010","volume":"74","author":"Blencowe","year":"2013","journal-title":"Pediatr. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1038\/s41372-021-01015-8","article-title":"80 Years of vision: Preventing blindness from retinopathy of prematurity","volume":"41","author":"Wood","year":"2021","journal-title":"J. Perinatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e057864","DOI":"10.1136\/bmjopen-2021-057864","article-title":"Costs associated with retinopathy of prematurity: A systematic review and meta-analysis","volume":"12","author":"Gyllensten","year":"2022","journal-title":"BMJ Open"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"270","DOI":"10.4103\/sjopt.sjopt_276_21","article-title":"Late sequelae of retinopathy of prematurity in adolescence and adulthood","volume":"36","author":"Ozdemir","year":"2022","journal-title":"Saudi J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S140","DOI":"10.1016\/j.ghir.2004.03.030","article-title":"Pathogenesis of retinopathy of prematurity","volume":"14","author":"Smith","year":"2004","journal-title":"Growth Horm. IGF Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.jaapos.2017.03.006","article-title":"Investigation of the effect of hemoglobin F and A levels on development of retinopathy of prematurity","volume":"21","author":"Erdol","year":"2017","journal-title":"J. AAPOS"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1167\/iovs.18-25525","article-title":"Discovering Mechanisms in the Changing and Diverse Pathology of Retinopathy of Prematurity: The Weisenfeld Award Lecture","volume":"60","author":"Hartnett","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e91","DOI":"10.1111\/aos.14852","article-title":"Ranibizumab in retinopathy of prematurity\u2014One-year follow-up of ophthalmic outcomes and two-year follow-up of neurodevelopmental outcomes from the CARE-ROP study","volume":"100","author":"Stahl","year":"2022","journal-title":"Acta Ophthalmol."},{"key":"ref_11","first-page":"CD009734","article-title":"Anti-vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity","volume":"2","author":"Sankar","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1001\/jama.2022.10564","article-title":"Effect of Intravitreal Aflibercept vs Laser Photocoagulation on Treatment Success of Retinopathy of Prematurity: The FIREFLEYE Randomized Clinical Trial","volume":"328","author":"Stahl","year":"2022","journal-title":"JAMA"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Chang, Y.H., Chien, L.N., Chen, W.T., and Lin, I.C. (2022). Comparison of risks of arterial thromboembolic events and glaucoma with ranibizumab and aflibercept intravitreous injection: A nationwide population-based cohort study. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0267088"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.ophtha.2020.07.062","article-title":"Risk of Systemic Adverse Events after Intravitreal Bevacizumab, Ranibizumab, and Aflibercept in Routine Clinical Practice","volume":"128","author":"Maloney","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0161-6420(91)32343-1","article-title":"Visual acuity in infants after vitrectomy for severe retinopathy of prematurity","volume":"98","author":"Quinn","year":"1991","journal-title":"Ophthalmology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/sj.eye.6702939","article-title":"Anatomical and visual outcome of stages 4 and 5 retinopathy of prematurity","volume":"23","author":"Shah","year":"2009","journal-title":"Eye"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1080\/17469899.2019.1596026","article-title":"A review of treatment for retinopathy of prematurity","volume":"14","author":"Hansen","year":"2019","journal-title":"Expert. Rev. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1016\/j.ophtha.2009.04.026","article-title":"Simultaneous analyses of vitreous levels of 27 cytokines in eyes with retinopathy of prematurity","volume":"116","author":"Sato","year":"2009","journal-title":"Ophthalmology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3595","DOI":"10.1167\/iovs.05-1522","article-title":"Potential role of microglia in retinal blood vessel formation","volume":"47","author":"Checchin","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/nm877","article-title":"Leukocytes mediate retinal vascular remodeling during development and vaso-obliteration in disease","volume":"9","author":"Ishida","year":"2003","journal-title":"Nat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.siny.2011.08.007","article-title":"Perinatal infection, inflammation, and retinopathy of prematurity","volume":"17","author":"Lee","year":"2012","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s12974-017-0943-1","article-title":"Retinopathy of prematurity: Inflammation, choroidal degeneration, and novel promising therapeutic strategies","volume":"14","author":"Rivera","year":"2017","journal-title":"J. Neuroinflammation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1046\/j.1365-2249.2002.01817.x","article-title":"Neonatal dendritic cells are intrinsically biased against Th-1 immune responses","volume":"128","author":"Langrish","year":"2002","journal-title":"Clin. Exp. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4312","DOI":"10.4049\/jimmunol.166.7.4312","article-title":"Regulatory activity of autocrine IL-10 on dendritic cell functions","volume":"166","author":"Corinti","year":"2001","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Nguyen, M., Leuridan, E., Zhang, T., De Wit, D., Willems, F., Van Damme, P., Goldman, M., and Goriely, S. (2010). Acquisition of adult-like TLR4 and TLR9 responses during the first year of life. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010407"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1007\/s10875-015-0128-6","article-title":"An impaired inflammatory cytokine response to gram-negative LPS in human neonates is associated with the defective TLR-mediated signaling pathway","volume":"35","author":"Li","year":"2015","journal-title":"J. Clin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1189\/jlb.0912468","article-title":"Neutrophil and endothelial adhesive function during human fetal ontogeny","volume":"93","author":"Nussbaum","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1189\/jlb.70.6.969","article-title":"Mechanisms underlying reduced responsiveness of neonatal neutrophils to distinct chemoattractants","volume":"70","author":"Weinberger","year":"2001","journal-title":"J. Leukoc. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Panda, S.K., Kumar, S., Tupperwar, N.C., Vaidya, T., George, A., Rath, S., Bal, V., and Ravindran, B. (2012). Chitohexaose activates macrophages by alternate pathway through TLR4 and blocks endotoxemia. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002717"},{"key":"ref_30","unstructured":"Acharya, S., Das, P., and Agarwaal, B. (2020). Novel Immunodulating Small. (PCT\/US2023\/022481), Molecules. Patent."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"108716","DOI":"10.1016\/j.exer.2021.108716","article-title":"TLR2 signaling contributes to the angiogenesis of oxygen-induced retinopathy","volume":"210","author":"Sun","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Amankwa, C.E., Gondi, S.R., Dibas, A., Weston, C., Funk, A., Nguyen, T., Nguyen, K.T., Ellis, D.Z., and Acharya, S. (2021). Novel Thiol Containing Hybrid Antioxidant-Nitric Oxide Donor Small Molecules for Treatment of Glaucoma. Antioxidants, 10.","DOI":"10.3390\/antiox10040575"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hinkle, L., Le, D., Nguyen, T., Tran, V., Amankwa, C.E., Weston, C., Shen, H., Nguyen, K.T., Rahimi, M., and Acharya, S. (2021). Nano encapsulated novel compound SA-10 with therapeutic activity in both acute and chronic murine hindlimb ischemia models. Nanomed. Nanotechnol. Biol. Med., 35.","DOI":"10.1016\/j.nano.2021.102400"},{"key":"ref_34","first-page":"37","article-title":"Nanoencapsulated hybrid compound SA-2 with long-lasting intraocular pressure-lowering activity in rodent eyes","volume":"27","author":"Stankowska","year":"2021","journal-title":"Mol. Vis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1161\/ATVBAHA.122.318079","article-title":"CD8+ T Cells Promote Pathological Angiogenesis in Ocular Neovascular Disease","volume":"43","author":"Deliyanti","year":"2023","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_36","first-page":"2027","article-title":"The contribution of T cells to retinopathy of prematurity in mice","volume":"54","author":"Talia","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_37","first-page":"1716","article-title":"The prognostic value of lymphocyte-to-monocyte ratio in retinopathy of prematurity","volume":"10","author":"Hu","year":"2017","journal-title":"Int. J. Ophthalmol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1007\/s00417-022-05902-4","article-title":"Blood neutrophil-to-lymphocyte ratio as a risk factor in treatment for retinopathy of prematurity","volume":"261","author":"Obata","year":"2023","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"985","DOI":"10.3345\/kjp.2010.53.12.985","article-title":"Neonatal innate immunity and Toll-like receptor","volume":"53","author":"Yoon","year":"2010","journal-title":"Korean J. Pediatr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.molmed.2007.09.002","article-title":"Signaling to NF-kappaB by Toll-like receptors","volume":"13","author":"Kawai","year":"2007","journal-title":"Trends Mol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"17590914221136365","DOI":"10.1177\/17590914221136365","article-title":"Multitarget Activities of Muller Glial Cells and Low-Density Lipoprotein Receptor-Related Protein 1 in Proliferative Retinopathies","volume":"14","author":"Sanchez","year":"2022","journal-title":"ASN Neuro"},{"key":"ref_42","first-page":"1907","article-title":"Toll-like receptor 4 contributes to retinal ischemia\/reperfusion injury","volume":"16","author":"Dvoriantchikova","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12974-023-02712-1","article-title":"Endothelial Toll-like receptor 4 is required for microglia activation in the murine retina after systemic lipopolysaccharide exposure","volume":"20","author":"Tsioti","year":"2023","journal-title":"J. Neuroinflammation"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"108557","DOI":"10.1016\/j.exer.2021.108557","article-title":"Loss of TLR4 in endothelial cells but not Muller cells protects the diabetic retina","volume":"206","author":"Seidel","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Li, Y., Deng, S.L., Lian, Z.X., and Yu, K. (2019). Roles of Toll-Like Receptors in Nitroxidative Stress in Mammals. Cells, 8.","DOI":"10.3390\/cells8060576"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Li, P., and Chang, M. (2021). Roles of PRR-Mediated Signaling Pathways in the Regulation of Oxidative Stress and Inflammatory Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147688"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Canton, M., Sanchez-Rodriguez, R., Spera, I., Venegas, F.C., Favia, M., Viola, A., and Castegna, A. (2021). Reactive Oxygen Species in Macrophages: Sources and Targets. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.734229"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7140496","DOI":"10.1155\/2020\/7140496","article-title":"Two Faces of Heme Catabolic Pathway in Newborns: A Potential Role of Bilirubin and Carbon Monoxide in Neonatal Inflammatory Diseases","volume":"2020","author":"Osiak","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1053\/j.semperi.2019.05.009","article-title":"Pharmacologic interventions for the prevention and treatment of retinopathy of prematurity","volume":"43","author":"Aranda","year":"2019","journal-title":"Semin. Perinatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"AB038","DOI":"10.21037\/aes.2019.AB038","article-title":"AB038. Pathological neovascularization in retinopathy of prematurity is regulated by heme-derived iron trafficking","volume":"4","author":"Agnihotri","year":"2020","journal-title":"Ann. Eye Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"44","DOI":"10.5005\/jp-journals-11002-0025","article-title":"Role of the Endothelium in Neonatal Diseases","volume":"1","author":"Maheshwari","year":"2022","journal-title":"Newborn"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Wang, Y., Wang, Y., Wang, X., Ma, Y., Li, Z., and Di, Y. (2022). LncRNA TUG1 Promotes Apoptosis, Invasion, and Angiogenesis of Retinal Endothelial Cells in Retinopathy of Prematurity via MiR-145-5p. Front. Med., 9.","DOI":"10.3389\/fmed.2022.803214"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Chen, S., Sun, Q., Sun, D., Willette-Brown, J., Anderson, M.J., Gu, Q., Lewandoski, M., Hu, Y., Zhu, F., and Wei, F. (2020). C-CBL is required for inhibition of angiogenesis through modulating JAK2\/STAT3 activity in ROP development. Biomed. Pharmacother., 132.","DOI":"10.1016\/j.biopha.2020.110856"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1634\/theoncologist.11-7-753","article-title":"Tyrosine kinase inhibitors of vascular endothelial growth factor receptors in clinical trials: Current status and future directions","volume":"11","author":"Morabito","year":"2006","journal-title":"Oncologist"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13045-019-0718-5","article-title":"Recent advances on anti-angiogenesis receptor tyrosine kinase inhibitors in cancer therapy","volume":"12","author":"Qin","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Kong, H.B., Zheng, G.Y., He, B.M., Zhang, Y., and Zhou, Q. (2021). Clinical Efficacy and Safety of Propranolol in the Prevention and Treatment of Retinopathy of Prematurity: A Meta-Analysis of Randomized Controlled Trials. Front. Pediatr., 9.","DOI":"10.3389\/fped.2021.631673"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Filippi, L., Cavallaro, G., Berti, E., Padrini, L., Araimo, G., Regiroli, G., Raffaeli, G., Bozzetti, V., Tagliabue, P., and Tomasini, B. (2019). Propranolol 0.2% Eye Micro-Drops for Retinopathy of Prematurity: A Prospective Phase IIB Study. Front. Pediatr., 7.","DOI":"10.3389\/fped.2019.00180"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1007\/s10792-022-02576-z","article-title":"Systemic biomarkers of retinopathy of prematurity in preterm babies","volume":"43","author":"Sehgal","year":"2023","journal-title":"Int. Ophthalmol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ghir.2017.11.006","article-title":"Increased postnatal concentrations of pro-inflammatory cytokines are associated with reduced IGF-I levels and retinopathy of prematurity","volume":"39","author":"Hellgren","year":"2018","journal-title":"Growth Horm. IGF Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1007\/s00417-009-1066-x","article-title":"Suppression of retinal neovascularization by the iNOS inhibitor aminoguanidine in mice of oxygen-induced retinopathy","volume":"247","author":"Zhang","year":"2009","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"64944","DOI":"10.7554\/eLife.64944","article-title":"eNOS-induced vascular barrier disruption in retinopathy by c-Src activation and tyrosine phosphorylation of VE-cadherin","volume":"10","author":"Ninchoji","year":"2021","journal-title":"Elife"},{"key":"ref_62","first-page":"222","article-title":"Reduced Severity of Oxygen-Induced Retinopathy in eNOS-Deficient Mice","volume":"42","author":"Brooks","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Mueller-Buehl, A.M., Tsai, T., Hurst, J., Theiss, C., Peters, L., Hofmann, L., Herms, F., Kuehn, S., Schnichels, S., and Joachim, S.C. (2021). Reduced Retinal Degeneration in an Oxidative Stress Organ Culture Model through an iNOS-Inhibitor. Biology, 10.","DOI":"10.3390\/biology10050383"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3987","DOI":"10.1523\/JNEUROSCI.22-10-03987.2002","article-title":"Inducible nitric oxide synthase mediates retinal apoptosis in ischemic proliferative retinopathy","volume":"22","author":"Sennlaub","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_65","first-page":"2793","article-title":"Normal Retina Contains Resident Plasmacytoid Dendritic Cells That Increase in a Mouse Model of Retinopathy of Prematurity","volume":"61","author":"Qiu","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.bbi.2004.01.004","article-title":"The influence of systemic inflammation on inflammation in the brain: Implications for chronic neurodegenerative disease","volume":"18","author":"Perry","year":"2004","journal-title":"Brain Behav. Immun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6419","DOI":"10.1167\/iovs.17-21931","article-title":"Systemic Inflammation-Associated Proteins and Retinopathy of Prematurity in Infants Born Before the 28th Week of Gestation","volume":"58","author":"Holm","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7590350","DOI":"10.1155\/2018\/7590350","article-title":"Macrophage Functions and Regulation: Roles in Diseases and Implications in Therapeutics","volume":"2018","author":"Hu","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_69","first-page":"4291","article-title":"Dendritic cells-mediated polarization of retinal macrophages in human diabetic retina","volume":"56","author":"Baban","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Chakravarthy, H., Beli, E., Navitskaya, S., O\u2019Reilly, S., Wang, Q., Kady, N., Huang, C., Grant, M.B., and Busik, J.V. (2016). Imbalances in Mobilization and Activation of Pro-Inflammatory and Vascular Reparative Bone Marrow-Derived Cells in Diabetic Retinopathy. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146829"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/16\/1371\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:38:11Z","timestamp":1760110691000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/16\/1371"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,17]]},"references-count":70,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["cells13161371"],"URL":"https:\/\/doi.org\/10.3390\/cells13161371","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,17]]}}}