{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T19:52:20Z","timestamp":1781639540868,"version":"3.54.5"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Aydin Adnan Menderes University"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Graefes Arch Clin Exp Ophthalmol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To investigate the ocular effects of prolactin elevation induced by anti-dopaminergic agents used for diabetic gastroparesis, including metoclopramide (MCP), trimethobenzamide (TMB), and domperidone (DOM), on intraocular pressure (IOP), tear production, and retinal angiogenesis-related markers in a streptozotocin-induced diabetic rat model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Fifty Wistar rats were randomly divided into five groups (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910 each): control, diabetes mellitus (DM), and DM treated with MCP, TMB, and DOM. Six weeks after diabetes induction, treatments were administered twice daily for two weeks. IOP and tear production (Schirmer test) were measured before enucleation. Retinal tissues were immunohistochemically analyzed for expression of the prolactin receptor, vascular endothelial growth factor (VEGF), and CD31. Staining intensity and the percentage of positive cells were semi-quantitatively scored, and mean values were compared among groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      IOP and tear production showed no significant intergroup differences. Retinal staining was most prominent in the ganglion cell layer; therefore, this region was analyzed in detail. Prolactin receptor expression was significantly increased in all treatment groups compared with the diabetic and control groups (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). VEGF and CD31 scores were elevated in the diabetic group but decreased with MCP, TMB, and DOM (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Prolactin-elevating antidopaminergic agents (MCP, TMB, and DOM) were associated with reduced immunoreactivity for VEGF and CD31 and increased expression of the prolactin receptor in the diabetic retina, without adverse effects on IOP or tear production. These findings warrant further investigation, including functional vascular assessments, to clarify their potential relevance in diabetic retinopathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00417-026-07173-9","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:10:05Z","timestamp":1772169005000},"page":"1619-1626","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic potential of prolactin-releasing anti-dopaminergic agents in experimental diabetic retinopathy model"],"prefix":"10.1007","volume":"264","author":[{"given":"Kubra","family":"Peker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse Ipek Akyuz","family":"Unsal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Meteoglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erol","family":"Erkan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinan","family":"Bekmez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayime Aydin","family":"Eroglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imran Kurt","family":"Omurlu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Turhan","family":"Dost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buket","family":"Demirci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"issue":"2","key":"7173_CR1","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s10517-021-05191-7","volume":"171","author":"MA Darenskaya","year":"2021","unstructured":"Darenskaya MA, Kolesnikova LI, Kolesnikov SI (2021) Oxidative Stress: Pathogenetic Role in Diabetes Mellitus and Its Complications and Therapeutic Approaches to Correction. Bull Exp Biol Med 171(2):179\u2013189. https:\/\/doi.org\/10.1007\/s10517-021-05191-7","journal-title":"Bull Exp Biol Med"},{"issue":"3","key":"7173_CR2","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1097\/MOH.0000000000000239","volume":"23","author":"P Lertkiatmongkol","year":"2016","unstructured":"Lertkiatmongkol P, Liao D, Mei H et al (2016) Endothelial functions of platelet\/endothelial cell adhesion molecule-1 (CD31). Curr Opin Hematol 23(3):253\u2013259. https:\/\/doi.org\/10.1097\/MOH.0000000000000239","journal-title":"Curr Opin Hematol"},{"key":"7173_CR3","doi-asserted-by":"publisher","first-page":"994898","DOI":"10.3389\/fendo.2022.994898","volume":"13","author":"J Triebel","year":"2022","unstructured":"Triebel J, Bertsch T, Clapp C (2022) Prolactin and vasoinhibin are endogenous players in diabetic retinopathy revisited. Front Endocrinol (Lausanne) 13:994898. https:\/\/doi.org\/10.3389\/fendo.2022.994898","journal-title":"Front Endocrinol (Lausanne)"},{"key":"7173_CR4","doi-asserted-by":"publisher","first-page":"2291","DOI":"10.1172\/JCI34508","volume":"118","author":"C Garc\u00eda","year":"2008","unstructured":"Garc\u00eda C, Aranda J, Arnold E et al (2008) Vasoinhibins prevent retinal vasopermeability associated with diabetic retinopathy in rats via protein phosphatase 2A-dependent eNOS inactivation. J Clin Invest 118:2291\u20132300. https:\/\/doi.org\/10.1172\/JCI34508","journal-title":"J Clin Invest"},{"issue":"4","key":"7173_CR5","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1111\/j.1365-2036.2004.01867.x","volume":"19","author":"M Tonini","year":"2004","unstructured":"Tonini M, Cipollina L, Poluzzi E et al (2004) Review article: Clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics. Aliment Pharmacol Ther 19(4):379\u2013390. https:\/\/doi.org\/10.1111\/j.1365-2036.2004.01867.x","journal-title":"Aliment Pharmacol Ther"},{"key":"7173_CR6","doi-asserted-by":"publisher","unstructured":"Isaacson SH, Dewey RB Jr, Pahwa R et al (2022) How to manage the initiation of apomorphine therapy without antiemetic pretreatment: A review of the literature. Clin Park Relat Disord. 2022;19;8:100174. https:\/\/doi.org\/10.1016\/j.prdoa.2022.100174","DOI":"10.1016\/j.prdoa.2022.100174"},{"issue":"2","key":"7173_CR7","doi-asserted-by":"publisher","first-page":"143","DOI":"10.5056\/jnm23100","volume":"30","author":"YX Zhang","year":"2024","unstructured":"Zhang YX, Zhang YJ, Li M et al (2024) Common Pathophysiological Mechanisms and Treatment of Diabetic Gastroparesis. J Neurogastroenterol Motil 30(2):143\u2013155. https:\/\/doi.org\/10.5056\/jnm23100PMID: 38576367; PMCID: PMC10999838","journal-title":"J Neurogastroenterol Motil"},{"key":"7173_CR8","doi-asserted-by":"publisher","unstructured":"Yoo TK, Oh E (2019) Diabetes mellitus is associated with dry eye syndrome: a meta-analysis Int Ophthalmol. 39(11):2611\u20132620. https:\/\/doi.org\/10.1007\/s10792-019-01110-y","DOI":"10.1007\/s10792-019-01110-y"},{"issue":"5","key":"7173_CR9","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1016\/S0161-6420(03)00075-7","volume":"110","author":"A Hennis","year":"2003","unstructured":"Hennis A, Wu SY, Nemesure B et al (2003) Hypertension, diabetes, and longitudinal changes in intraocular pressure. Ophthalmology 110(5):908\u2013914. https:\/\/doi.org\/10.1016\/S0161-6420(03)00075-7","journal-title":"Ophthalmology"},{"issue":"4","key":"7173_CR10","doi-asserted-by":"publisher","first-page":"e78","DOI":"10.1002\/cpz1.78","volume":"1","author":"BL Furman","year":"2021","unstructured":"Furman BL (2021) Streptozotocin-induced diabetic models in mice and rats. Curr Protoc 1(4):e78. https:\/\/doi.org\/10.1002\/cpz1.78","journal-title":"Curr Protoc"},{"issue":"1","key":"7173_CR11","doi-asserted-by":"publisher","first-page":"809","DOI":"10.3892\/mmr.2017.7947","volume":"17","author":"KJ Chien","year":"2018","unstructured":"Chien KJ, Horng CT, Huang YS et al (2018) Effects of Lycium barbarum (goji berry) on dry eye disease in rats. Mol Med Rep 17(1):809\u2013818. https:\/\/doi.org\/10.3892\/mmr.2017.7947","journal-title":"Mol Med Rep"},{"issue":"4","key":"7173_CR12","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1111\/ceo.12696","volume":"44","author":"DSW Ting","year":"2016","unstructured":"Ting DSW, Cheung GCM, Wong TY (2016) Diabetic retinopathy: global prevalence, major risk factors, screening practices and public health challenges: a review. Clin Exp Ophthalmol 44(4):260\u2013277. https:\/\/doi.org\/10.1111\/ceo.12696","journal-title":"Clin Exp Ophthalmol"},{"issue":"11","key":"7173_CR13","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1016\/j.ophtha.2021.04.027","volume":"128","author":"ZL Teo","year":"2021","unstructured":"Teo ZL, Tham Y-C, Yu M et al (2021) Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis. Ophthalmology 128(11):1580\u20131591. https:\/\/doi.org\/10.1016\/j.ophtha.2021.04.027","journal-title":"Ophthalmology"},{"issue":"1","key":"7173_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.preteyeres.2006.09.002","volume":"26","author":"SX Zhang","year":"2007","unstructured":"Zhang SX, Ma J (2007) Ocular neovascularization: Implication of endogenous angiogenic inhibitors and potential therapy. Prog Retin Eye Res 26(1):1\u201337. https:\/\/doi.org\/10.1016\/j.preteyeres.2006.09.002","journal-title":"Prog Retin Eye Res"},{"issue":"4","key":"7173_CR15","doi-asserted-by":"publisher","first-page":"e13091","DOI":"10.1111\/jne.13091","volume":"34","author":"E Ad\u00e1n-Castro","year":"2022","unstructured":"Ad\u00e1n-Castro E, Siqueiros-M\u00e1rquez L, Ram\u00edrez-Hern\u00e1ndez G et al (2022) Sulpiride-induced hyperprolactinaemia increases retinal vasoinhibin and protects against diabetic retinopathy in rats. J Neuroendocrinol 34(4):e13091. https:\/\/doi.org\/10.1111\/jne.13091Epub 2022 Jan 25","journal-title":"J Neuroendocrinol"},{"issue":"9","key":"7173_CR16","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1167\/tvst.9.9.27","volume":"9","author":"CD Nu\u00f1ez-Amaro","year":"2020","unstructured":"Nu\u00f1ez-Amaro CD, Moreno-Vega AI, Adan-Castro E et al (2020) Levosulpiride Increases the Levels of Prolactin and Antiangiogenic Vasoinhibin in the Vitreous of Patients with Proliferative Diabetic Retinopathy. Transl Vis Sci Technol 9(9):27. https:\/\/doi.org\/10.1167\/tvst.9.9.27PMID: 32879783; PMCID: PMC7442881","journal-title":"Transl Vis Sci Technol"},{"issue":"3","key":"7173_CR17","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1038\/s41433-023-02715-5","volume":"38","author":"CD N\u00fa\u00f1ez-Amaro","year":"2024","unstructured":"N\u00fa\u00f1ez-Amaro CD, L\u00f3pez M, Ad\u00e1n-Castro E et al (2024) Levosulpiride for the treatment of diabetic macular oedema: a phase 2 randomized clinical trial. Eye (Lond) 38(3):520\u2013528. https:\/\/doi.org\/10.1038\/s41433-023-02715-5","journal-title":"Eye (Lond)"},{"issue":"2","key":"7173_CR18","doi-asserted-by":"publisher","first-page":"355","DOI":"10.4103\/ijem.IJEM_555_16","volume":"21","author":"MS Kuchay","year":"2017","unstructured":"Kuchay MS, Mithal A (2017) Levosulpiride and serum prolactin levels. Indian J Endo crinol Metab 21(2):355\u2013358. https:\/\/doi.org\/10.4103\/ijem.IJEM_555_16","journal-title":"Indian J Endo crinol Metab"},{"issue":"3","key":"7173_CR19","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/labinvest.2015.135","volume":"96","author":"N D\u00edaz-Lezama","year":"2016","unstructured":"D\u00edaz-Lezama N, Wu Z, Ad\u00e1n-Castro E et al (2016) Diabetes enhances the efficacy of AAV2 vectors in the retina: therapeutic effect of AAV2 encoding vasoinhibin and soluble VEGF receptor 1. Lab Investig 96(3):283\u2013295. https:\/\/doi.org\/10.1038\/labinvest.2015.135","journal-title":"Lab Investig"},{"issue":"12","key":"7173_CR20","doi-asserted-by":"publisher","first-page":"8944","DOI":"10.1167\/iovs.11-8190","volume":"52","author":"M Ramirez","year":"2011","unstructured":"Ramirez M, Wu Z, Moreno-Carranza B et al (2011) Vasoinhibin gene transfer by adenoassociated virus type 2 protects against VEGF- and diabetes-induced retinal vasopermeability. Invest OphthalmolVisual Sci 52(12):8944\u20138950. https:\/\/doi.org\/10.1167\/iovs.11-8190","journal-title":"Invest OphthalmolVisual Sci"},{"issue":"1","key":"7173_CR21","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1093\/cvr\/cvs108","volume":"94","author":"L Liu","year":"2012","unstructured":"Liu L, Shi GP (2012) CD31: Beyond a marker for endothelial cells. Cardiovasc Res 94(1):3\u20135. https:\/\/doi.org\/10.1093\/cvr\/cvs108","journal-title":"Cardiovasc Res"},{"issue":"5","key":"7173_CR22","doi-asserted-by":"publisher","first-page":"669","DOI":"10.14670\/HH-18-825","volume":"40","author":"M Komolkriengkrai","year":"2025","unstructured":"Komolkriengkrai M, Matsathit U, Sirinupong N et al (2025) The effectiveness of edible bird\u2019s nest in lowering VEGF, CD31, and PDGFR-\u03b2 levels in diabetic retinopathy in rats with type 1 diabetes. Histol Histopathol 40(5):669\u2013678. https:\/\/doi.org\/10.14670\/HH-18-825","journal-title":"Histol Histopathol"},{"issue":"1","key":"7173_CR23","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1172\/JCI119129","volume":"99","author":"PJ Newman","year":"1997","unstructured":"Newman PJ (1997) The biology of PECAM-1. J Clin Invest 99(1):3\u20138. https:\/\/doi.org\/10.1172\/JCI119129","journal-title":"J Clin Invest"},{"issue":"9","key":"7173_CR24","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1080\/02713683.2024.2349642","volume":"49","author":"S Duan","year":"2024","unstructured":"Duan S, Tian B, Huang G et al (2024) A Rabbit Dry Eye Model Induced by Subcutaneous Scopolamine. Curr Eye Res 49(9):905\u2013913. https:\/\/doi.org\/10.1080\/02713683.2024.2349642","journal-title":"Curr Eye Res"}],"container-title":["Graefe's Archive for Clinical and Experimental Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00417-026-07173-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00417-026-07173-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00417-026-07173-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:58:54Z","timestamp":1781636334000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00417-026-07173-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,27]]},"references-count":24,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["7173"],"URL":"https:\/\/doi.org\/10.1007\/s00417-026-07173-9","relation":{},"ISSN":["0721-832X","1435-702X"],"issn-type":[{"value":"0721-832X","type":"print"},{"value":"1435-702X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,27]]},"assertion":[{"value":"2 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 January 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 February 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All applicable international, national, and institutional guidelines for the care and use of animals were followed. The study was approved by the Aydin Adnan Menderes University Animal Experiments Local Ethics Committee (HADYEK 64583101\/2024\/04).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable. This study does not involve human participants.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"Aydin Adnan Menderes University for Animal Experiments (HADYEK 64583101\/2024\/04).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Approved by the following research ethics committee"}},{"value":"The authors declare that they have no affiliations with or involvement in any organization or entity with a financial interest (such as honoraria; educational grants; participation in speakers\u2019 bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements) or a non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}