{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T15:34:25Z","timestamp":1773675265822,"version":"3.50.1"},"reference-count":24,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Fungal infections can pose great threat to sight. Immediate treatment is usually required; antifungal agents are widely accepted and are effective in most cases. The present experimental study aims to investigate the probable effects of intravitreal injection of antifungal agents on the structure and mechanical properties of the surface of peripheral blood erythrocytes. Methods: Nine albino New Zealand white rabbits, aged five months old, were chosen for the experiment. Solutions of micafungin, voriconazole, or balanced salt solution (BSS) were injected into the midvitreous. Animals were divided into two experimental groups and one control group. Blood sampling from an intravenous (IV) line was performed after 10 days from the last IV injection. An atomic force microscope (AFM) was used to study the structural and mechanical properties of cell surfaces. Results: The analysis results showed that the parameters of the cytoskeleton\u2019s spatial organization changed insignificantly with the antifungal drug treatment. Conclusions: Our findings suggest that locally administered antifungal drugs can cause significant changes to the structure and frictional properties of the erythrocyte surface. These effects occur in the long-term period after administration of the drugs and represent a potential possibility for violation of blood supply to tissues, and the further development of negative side effects.<\/jats:p>","DOI":"10.3390\/ijms231810464","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T22:53:46Z","timestamp":1663023226000},"page":"10464","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Effects of Intravitreal Administration of Antifungal Drugs on the Structure and Mechanical Properties Peripheral Blood Erythrocyte Surface in Rabbits"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8516-0884","authenticated-orcid":false,"given":"Maria N.","family":"Starodubtseva","sequence":"first","affiliation":[{"name":"Institute of Radiobiology of the NAS of Belarus, 4, Fedyuninskogo St., 246007 Gomel, Belarus"},{"name":"Medical Department, Gomel State University, 5, Lange St., 246000 Gomel, Belarus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6309-8410","authenticated-orcid":false,"given":"Sofia","family":"Karachrysafi","sequence":"additional","affiliation":[{"name":"Laboratory of Histology, Embryology, Medical Department, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6365-3856","authenticated-orcid":false,"given":"Nastassia M.","family":"Shkliarava","sequence":"additional","affiliation":[{"name":"Institute of Radiobiology of the NAS of Belarus, 4, Fedyuninskogo St., 246007 Gomel, Belarus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina A.","family":"Chelnokova","sequence":"additional","affiliation":[{"name":"Institute of Radiobiology of the NAS of Belarus, 4, Fedyuninskogo St., 246007 Gomel, Belarus"},{"name":"Medical Department, Gomel State University, 5, Lange St., 246000 Gomel, Belarus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3325-2752","authenticated-orcid":false,"given":"Dimitrios","family":"Kavvadas","sequence":"additional","affiliation":[{"name":"Laboratory of Histology, Embryology, Medical Department, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyriaki","family":"Papadopoulou","sequence":"additional","affiliation":[{"name":"Laboratory of Histology, Embryology, Medical Department, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paraskevi","family":"Samara","sequence":"additional","affiliation":[{"name":"MRes Applied Health Research, Department of Health Sciences, University of Leicester, Leicester LE1 7RH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1064-0290","authenticated-orcid":false,"given":"Vasileios","family":"Papaliagkas","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Health Sciences, International Hellenic University, 57400 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia","family":"Sioga","sequence":"additional","affiliation":[{"name":"Laboratory of Histology, Embryology, Medical Department, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasia","family":"Komnenou","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 57400 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasileios","family":"Karampatakis","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Ophthalmology, Medical Department, Faculty of Health Sciences, Aristotle University of Thessaloniki, 57400 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0709-5407","authenticated-orcid":false,"given":"Theodora","family":"Papamitsou","sequence":"additional","affiliation":[{"name":"Laboratory of Histology, Embryology, Medical Department, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bongomin, F., Gago, S., Oladele, R.O., and Denning, D.W. (2017). Global and Multi-National Prevalence of Fungal Diseases-Estimate Precision. J. Fungi, 3.","DOI":"10.3390\/jof3040057"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Haseeb, A.A., Elhusseiny, A.M., Siddiqui, M.Z., Ahmad, K.T., and Sallam, A.B. (2021). Fungal Endophthalmitis: A Comprehensive Review. J. Fungi, 7.","DOI":"10.3390\/jof7110996"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Karachrysafi, S., Sioga, A., Komnenou, A., Karamitsos, A., Xioteli, M., Dori, I., Delis, G., Kofidou, E., Anastasiadou, P., and Sotiriou, S. (2020). Histological Effects of Intravitreal Injection of Antifungal Agents in New Zealand White Rabbits: An Electron Microscopic and Immunohistochemical Study. Pharmaceuticals, 13.","DOI":"10.3390\/ph13100267"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"336","DOI":"10.3389\/fmicb.2017.00336","article-title":"Antifungal Therapy for Systemic Mycosis and the Nanobiotechnology Era: Improving Efficacy, Biodistribution and Toxicity","volume":"8","author":"Souza","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1159\/000445582","article-title":"Anidulafungin-Induced Suicidal Erythrocyte Death","volume":"38","author":"Peter","year":"2016","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1111\/ctr.12834","article-title":"Adverse effects of voriconazole: Over a decade of use","volume":"30","author":"Levine","year":"2016","journal-title":"Clin. Transplant."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Borodich, F.M., and Jin, X. (2022). Mechanical Properties of the Cell Surface Layer Measured by Contact Atomic Force Microscopy. Contact Problems for Soft, Biological and Bioinspired Materials, Springer. Biologically-Inspired Systems.","DOI":"10.1007\/978-3-030-85175-0"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jbiomech.2018.11.017","article-title":"Nano- and microscale mechanical properties of erythrocytes in hereditary spherocytosis","volume":"83","author":"Starodubtseva","year":"2019","journal-title":"J. Biomech."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Wang, Y., and Wang, J. (2018). Friction Determination by Atomic Force Microscopy in Field of Biochemical Science. Micromachines, 9.","DOI":"10.3390\/mi9070313"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Braga, P., and Ricci, D. (2011). Normal and Pathological Erythrocytes Studied by Atomic Force Microscopy. Atomic Force Microscopy in Biomedical Research, Methods in Molecular Biology; Humana Press.","DOI":"10.1007\/978-1-61779-105-5"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.cis.2017.05.011","article-title":"Atomic force microscopy: From red blood cells to immunohaematology","volume":"249","author":"Yeow","year":"2017","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sergunova, V., Leesment, S., Kozlov, A., Inozemtsev, V., Platitsina, P., Lyapunova, S., Onufrievich, A., Polyakov, V., and Sherstyukova, E. (2022). Investigation of Red Blood Cells by Atomic Force Microscopy. Sensors, 22.","DOI":"10.3390\/s22052055"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s15010-017-1042-z","article-title":"Pharmacokinetics of antifungal drugs: Practical implications for optimized treatment of patients","volume":"45","author":"Bellmann","year":"2017","journal-title":"Infection"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5548","DOI":"10.1128\/AAC.00884-15","article-title":"In vitro study of the variable effects of proton pump inhibitors on voriconazole","volume":"59","author":"Niece","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_15","first-page":"584","article-title":"Micafungin-Induced Suicidal Erythrocyte Death Cell","volume":"39","author":"Peter","year":"2016","journal-title":"Physiol. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1742-6405-11-25","article-title":"Therapeutic drug monitoring of voriconazole: A case report of multiple drug interactions in a patient with an increased CYP2C19 activity","volume":"11","author":"Bouatou","year":"2014","journal-title":"AIDS Res. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"224701","DOI":"10.1063\/5.0048232","article-title":"Mechanical properties of anionic asymmetric bilayers from atomistic simulations","volume":"154","author":"Jiang","year":"2021","journal-title":"J. Chem. Phys."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6225","DOI":"10.1039\/D1CP04836H","article-title":"Elastic moduli of normal and cancer cell membranes revealed by molecular dynamics simulations","volume":"24","author":"Nguyen","year":"2022","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4027","DOI":"10.1128\/AAC.02300-12","article-title":"Intraocular penetration of intravenous micafungin in inflamed human eyes","volume":"57","author":"Mochizuki","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1167\/iovs.06-1362","article-title":"Clearance of intravitreal voriconazole","volume":"48","author":"Shen","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1001\/archopht.122.11.1687","article-title":"Intravitreal voriconazole: An electroretinographic and histopathologic study","volume":"122","author":"Gao","year":"2004","journal-title":"Arch. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s10633-005-7342-0","article-title":"Retinal function assessed by ERG before and after induction of ocular aspergillosis and treatment by the anti-fungal, micafungin, in rabbits","volume":"110","author":"Harrison","year":"2005","journal-title":"Doc. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.1007\/s11095-012-0721-9","article-title":"Simulating Intravitreal Injections in Anatomically Accurate Models for Rabbit, Monkey, and Human Eyes","volume":"29","author":"Missel","year":"2012","journal-title":"Pharm. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.exer.2015.05.003","article-title":"Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data","volume":"137","author":"Urtti","year":"2015","journal-title":"Exp. Eye Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10464\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:28:37Z","timestamp":1760142517000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10464"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,9]]},"references-count":24,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ijms231810464"],"URL":"https:\/\/doi.org\/10.3390\/ijms231810464","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,9]]}}}