{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T07:09:18Z","timestamp":1788764958681,"version":"build-2803163510"},"reference-count":48,"publisher":"Knowledge E DMCC","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["knepublishing.com"],"crossmark-restriction":true},"short-container-title":["JOVR"],"abstract":"<jats:p>Purpose: Diabetic retinopathy is marked by hyperglycemia-induced inflammation and chemokine signaling that drive immune cell infiltration and retinal damage. As bevacizumab offers limited benefit in some cases, targeting broader inflammatory pathways with agents like triamcinolone may enhance therapeutic outcomes.\nMethods: ARPE-19 cells exposed to hyperglycemic conditions (30 mM glucose) for 72 hours were treated with bevacizumab (0.3 mg\/ml), triamcinolone (1mg\/ml), or their combination. Cell proliferation was assessed using the MTT assay, while ELISA measured VEGF, MCP- 1, and CXCL10 secretion, and qRT-PCR analyzed CCR2 and CXCR3 gene expression. Three independent biological replicates were used in each experiment.\nResults: Hyperglycemia markedly increased cell proliferation after 24 and 48 hours (P &lt; 0.001). Bevacizumab or triamcinolone alone did not alter cell proliferation under hyperglycemic stress; however, their combined treatment significantly reduced proliferation (P &lt; 0.001). Hyperglycemia markedly elevated VEGF secretion (P &lt; 0.001), whereas bevacizumab, triamcinolone, and especially their combination significantly suppressed it (all P &lt; 0.05). All three treatment conditions significantly reduced MCP-1 levels (P &lt; 0.05), while only the combined therapy lowered CXCL10 secretion (P &lt; 0.01). Regarding chemokine receptors, both drugs individually downregulated CCR2 and CXCR3 expression, with the combination producing an additive inhibitory effect (CCR2: P &lt; 0.001; CXCR3: P &lt; 0.05).\nConclusion: These results reveal that triamcinolone may complement bevacizumab by targeting VEGF-independent inflammatory pathways, providing mechanistic insight into combination therapy for diabetic macular edema (DME), particularly in patients with persistent DME despite anti-VEGF monotherapy.<\/jats:p>","DOI":"10.18502\/jovr.v21.19302","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:21:28Z","timestamp":1788441688000},"page":"1-11","update-policy":"https:\/\/doi.org\/10.18502\/knecrossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic Insights into the Combined Anti-inflammatory Effects of Bevacizumab and Triamcinolone in Hyperglycemic Retinal Cells: Modulation of MCP-1, CXCL10, and Their Receptors"],"prefix":"10.18502","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2800-8998","authenticated-orcid":false,"given":"Zahra","family":"Souri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3814-8863","authenticated-orcid":false,"given":"Mohammad","family":"Malekahmadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7392-6056","authenticated-orcid":false,"given":"Farzad","family":"Pakdel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"7770","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"342824","doi-asserted-by":"crossref","unstructured":"1. 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M\u00fcller cell-derived VEGF is essential for diabetes-induced retinal inflammation and vascular leakage. Diabetes 2010;59:2297-2305.","DOI":"10.2337\/db09-1420"},{"key":"342850","doi-asserted-by":"crossref","unstructured":"27. Haritoglou C, Kook D, Neubauer A, Wolf A, Priglinger S, Strauss R, et al. Intravitreal bevacizumab (Avastin) therapy for persistent diffuse diabetic macular edema. Retina 2006;26:999-1005.","DOI":"10.1097\/01.iae.0000247165.38655.bf"},{"key":"342851","doi-asserted-by":"crossref","unstructured":"28. Yozgat Z, Isik MU, Sabaner MC. One-year outcomes of aflibercept in treat-and-extend versus pro re nata regimens for bevacizumab-resistant diabetic macular edema: A realworld study. Ophthalmol Ther 2025;14:169-181.","DOI":"10.1007\/s40123-024-01067-x"},{"key":"342852","doi-asserted-by":"crossref","unstructured":"29. Bressler SB, Ayala AR, Bressler NM, Melia M, Qin H, Ferris FL 3rd, et al.; Diabetic Retinopathy Clinical Research Network. 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Am J Ophthalmol 2001;132:425-427.","DOI":"10.1016\/S0002-9394(01)01010-8"},{"key":"342855","doi-asserted-by":"crossref","unstructured":"32. Du Y, Miller CM, Kern TS. Hyperglycemia increases mitochondrial superoxide in retina and retinal cells. Free Radic Biol Med 2003;35:1491-1499.","DOI":"10.1016\/j.freeradbiomed.2003.08.018"},{"key":"342856","doi-asserted-by":"crossref","unstructured":"33. Kida T, Oku H, Osuka S, Horie T, Ikeda T. Hyperglycemiainduced VEGF and ROS production in retinal cells is inhibited by the mTOR inhibitor, rapamycin. Sci Rep 2021;11:1885.","DOI":"10.1038\/s41598-021-81482-3"},{"key":"342857","doi-asserted-by":"crossref","unstructured":"34. Park YJ, Ahn J, Kim TW, Park SJ, Joo K, Park KH, et al. Efficacy of bevacizumab for vitreous haemorrhage in proliferative diabetic retinopathy with prior complete panretinal photocoagulation. Eye (Lond) 2021;35:3056- 3063.","DOI":"10.1038\/s41433-020-01384-y"},{"key":"342858","doi-asserted-by":"crossref","unstructured":"35. Yu YY, Cheng Y, Chang LB, Xia HK, Li XX. Triamcinolone as an adjunct to the combination of anti-VEGF for the management of diabetic macular edema. Int J Ophthalmol 2021;14:869-874.","DOI":"10.18240\/ijo.2021.06.12"},{"key":"342859","doi-asserted-by":"crossref","unstructured":"36. Fazel F, Malekahmadi M, Feizi A, Oliya B, Tavakoli M, Fazel M. Suprachoroidal injection of triamcinolone acetonide plus intravitreal bevacizumab in diabetic macular edema: A randomized pilot trial. BMC Ophthalmol 2023;23:40.","DOI":"10.1186\/s12886-023-02790-y"},{"key":"342860","doi-asserted-by":"crossref","unstructured":"37. Boyer DS, Yoon YH, Belfort R Jr, Bandello F, Maturi RK, Augustin AJ, et al.; Ozurdex MEAD Study Group. Threeyear, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology 2014;121:1904-1914.","DOI":"10.1016\/j.ophtha.2014.04.024"},{"key":"342861","doi-asserted-by":"crossref","unstructured":"38. 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