Safety of anti-VEGF treatments in a diabetic rat model and retinal cell culture

Richard Filek,1 Phil Hooper,2,3 Tom G Sheidow,2,3 Hong Liu,3 Subrata Chakrabarti,1 Cindy ML Hutnik1–31Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada; 2Department of Ophthalmology, Western University, London, ON, Canada; 3Ivey Eye Institute,...

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Autores principales:	Filek R, Hooper P, Sheidow TG, Liu H, Chakrabarti S, Hutnik CML
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	diabetic macular edema diabetes retina anti-VEGF ranibizumab safety;cytotoxicity. Ophthalmology RE1-994
Acceso en línea:	https://doaj.org/article/cd5629ca4a9645dd8bffb3a31ab13040
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spelling	oai:doaj.org-article:cd5629ca4a9645dd8bffb3a31ab130402021-12-02T04:53:02ZSafety of anti-VEGF treatments in a diabetic rat model and retinal cell culture1177-5483https://doaj.org/article/cd5629ca4a9645dd8bffb3a31ab130402019-07-01T00:00:00Zhttps://www.dovepress.com/safety-of-anti-vegf-treatments-in-a-diabetic-rat-model-and-retinal-cel-peer-reviewed-article-OPTHhttps://doaj.org/toc/1177-5483Richard Filek,1 Phil Hooper,2,3 Tom G Sheidow,2,3 Hong Liu,3 Subrata Chakrabarti,1 Cindy ML Hutnik1–31Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada; 2Department of Ophthalmology, Western University, London, ON, Canada; 3Ivey Eye Institute, St. Joseph’s Health Care London, London, ON, CanadaPurpose: To analyze the safety of different concentrations of anti-VEGF on retinal cells.Methods: Non-diabetic and streptozotocin (STZ)-induced diabetic rats received intravitreal rat anti-VEGF injections that had final vitreous concentrations of 0, 0.0625, 0.125 (clinical dose), and 0.25 mg/mL. Rats were also injected with the clinical dose of ranibizumab. TUNEL assay was performed on sectioned eyes to evaluate apoptotic cells. In vitro, rat retinal cell cultures were exposed to 0, 0.0625, 0.125 (clinical dose), and 0.25 mg/mL of ranibizumab for 48 and 72 hrs. Cellular metabolic activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, necrosis by lactate dehydrogenase (LDH), and apoptosis by cell death enzyme-linked immunosorbent assay (ELISA).Results: Diabetic rats had a significant increase (p<0.03) in apoptotic cell death at half the clinical dose, at the clinical dose, and at double the clinical dose. In vitro, MTT showed a significant decrease (p<0.04) in cellular metabolic activity at the clinical dose and double the clinical dose compared to control at 48 and 72 hrs. LDH showed a significant increase (p<0.04) in necrosis at the clinical dose and double the clinical dose compared to control at 48 and 72 hrs. ELISA showed a significant increase (p<0.04) in apoptosis at half the clinical dose, at the clinical dose, and double the clinical dose, compared to control at 48 and 72 hrs.Conclusions: Anti-VEGF treatment may be potentially detrimental to the retina by decreasing cellular metabolic activity and increasing cytotoxicity of retinal cells. The results provide a cautionary note to monitor both the retina and optic nerve status in patients undergoing frequent injections.Keywords: diabetic macular edema, diabetes, retina, anti-VEGF, ranibizumab, safety, cytotoxicityFilek RHooper PSheidow TGLiu HChakrabarti SHutnik CMLDove Medical Pressarticlediabetic macular edemadiabetesretinaanti-VEGFranibizumabsafety;cytotoxicity.OphthalmologyRE1-994ENClinical Ophthalmology, Vol Volume 13, Pp 1097-1114 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	diabetic macular edema diabetes retina anti-VEGF ranibizumab safety;cytotoxicity. Ophthalmology RE1-994
spellingShingle	diabetic macular edema diabetes retina anti-VEGF ranibizumab safety;cytotoxicity. Ophthalmology RE1-994 Filek R Hooper P Sheidow TG Liu H Chakrabarti S Hutnik CML Safety of anti-VEGF treatments in a diabetic rat model and retinal cell culture
description	Richard Filek,1 Phil Hooper,2,3 Tom G Sheidow,2,3 Hong Liu,3 Subrata Chakrabarti,1 Cindy ML Hutnik1–31Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada; 2Department of Ophthalmology, Western University, London, ON, Canada; 3Ivey Eye Institute, St. Joseph’s Health Care London, London, ON, CanadaPurpose: To analyze the safety of different concentrations of anti-VEGF on retinal cells.Methods: Non-diabetic and streptozotocin (STZ)-induced diabetic rats received intravitreal rat anti-VEGF injections that had final vitreous concentrations of 0, 0.0625, 0.125 (clinical dose), and 0.25 mg/mL. Rats were also injected with the clinical dose of ranibizumab. TUNEL assay was performed on sectioned eyes to evaluate apoptotic cells. In vitro, rat retinal cell cultures were exposed to 0, 0.0625, 0.125 (clinical dose), and 0.25 mg/mL of ranibizumab for 48 and 72 hrs. Cellular metabolic activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, necrosis by lactate dehydrogenase (LDH), and apoptosis by cell death enzyme-linked immunosorbent assay (ELISA).Results: Diabetic rats had a significant increase (p<0.03) in apoptotic cell death at half the clinical dose, at the clinical dose, and at double the clinical dose. In vitro, MTT showed a significant decrease (p<0.04) in cellular metabolic activity at the clinical dose and double the clinical dose compared to control at 48 and 72 hrs. LDH showed a significant increase (p<0.04) in necrosis at the clinical dose and double the clinical dose compared to control at 48 and 72 hrs. ELISA showed a significant increase (p<0.04) in apoptosis at half the clinical dose, at the clinical dose, and double the clinical dose, compared to control at 48 and 72 hrs.Conclusions: Anti-VEGF treatment may be potentially detrimental to the retina by decreasing cellular metabolic activity and increasing cytotoxicity of retinal cells. The results provide a cautionary note to monitor both the retina and optic nerve status in patients undergoing frequent injections.Keywords: diabetic macular edema, diabetes, retina, anti-VEGF, ranibizumab, safety, cytotoxicity
format	article
author	Filek R Hooper P Sheidow TG Liu H Chakrabarti S Hutnik CML
author_facet	Filek R Hooper P Sheidow TG Liu H Chakrabarti S Hutnik CML
author_sort	Filek R
title	Safety of anti-VEGF treatments in a diabetic rat model and retinal cell culture
title_short	Safety of anti-VEGF treatments in a diabetic rat model and retinal cell culture
title_full	Safety of anti-VEGF treatments in a diabetic rat model and retinal cell culture
title_fullStr	Safety of anti-VEGF treatments in a diabetic rat model and retinal cell culture
title_full_unstemmed	Safety of anti-VEGF treatments in a diabetic rat model and retinal cell culture
title_sort	safety of anti-vegf treatments in a diabetic rat model and retinal cell culture
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/cd5629ca4a9645dd8bffb3a31ab13040
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Safety of anti-VEGF treatments in a diabetic rat model and retinal cell culture

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