Cargando…
Small extracellular vesicle-loaded bevacizumab reduces the frequency of intravitreal injection required for diabetic retinopathy
Diabetic retinopathy (DR) is associated with retinal neovascularization, hard exudates, inflammation, oxidative stress and cell death, leading to vision loss. Anti-vascular endothelial growth factor (Anti-VEGF) therapy through repeated intravitreal injections is an established treatment for reducing...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157735/ https://www.ncbi.nlm.nih.gov/pubmed/37153730 http://dx.doi.org/10.7150/thno.78426 |
_version_ | 1785036818590203904 |
---|---|
author | Reddy, Shivakumar K Ballal, Abhijna R Shailaja, S Seetharam, Raviraja N Raghu, Chandrashekar H Sankhe, Runali Pai, Kanthilatha Tender, Tenzin Mathew, Mary Aroor, Annayya Shetty, Ashok K Adiga, Shalini Devi, Vasudha Muttigi, Manjunatha S Upadhya, Dinesh |
author_facet | Reddy, Shivakumar K Ballal, Abhijna R Shailaja, S Seetharam, Raviraja N Raghu, Chandrashekar H Sankhe, Runali Pai, Kanthilatha Tender, Tenzin Mathew, Mary Aroor, Annayya Shetty, Ashok K Adiga, Shalini Devi, Vasudha Muttigi, Manjunatha S Upadhya, Dinesh |
author_sort | Reddy, Shivakumar K |
collection | PubMed |
description | Diabetic retinopathy (DR) is associated with retinal neovascularization, hard exudates, inflammation, oxidative stress and cell death, leading to vision loss. Anti-vascular endothelial growth factor (Anti-VEGF) therapy through repeated intravitreal injections is an established treatment for reducing VEGF levels in the retina for inhibiting neovascularization and leakage of hard exudates to prevent vision loss. Although anti-VEGF therapy has several clinical benefits, its monthly injection potentially causes devastating ocular complications, including trauma, intraocular hemorrhage, retinal detachment, endophthalmitis, etc. Methods: As mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) demonstrated safety in clinical studies, we have tested the efficacy of MSC-derived small EVs (MSC-sEVs) loaded anti-VEGF drug bevacizumab in a rat model of DR. Results: The study identified a clinically significant finding that sEV loaded with bevacizumab reduces the frequency of intravitreal injection required for treating diabetic retinopathy. The sustained effect is observed from the reduced levels of VEGF, exudates and leukostasis for more than two months following intravitreal injection of sEV loaded with bevacizumab, while bevacizumab alone could maintain reduced levels for about one month. Furthermore, retinal cell death was consistently lower in this period than only bevacizumab. Conclusion: This study provided significant evidence for the prolonged benefits of sEVs as a drug delivery system. Also, EV-mediated drug delivery systems could be considered for clinical application of retinal diseases as they maintain vitreous clarity in the light path due to their composition being similar to cells. |
format | Online Article Text |
id | pubmed-10157735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-101577352023-05-05 Small extracellular vesicle-loaded bevacizumab reduces the frequency of intravitreal injection required for diabetic retinopathy Reddy, Shivakumar K Ballal, Abhijna R Shailaja, S Seetharam, Raviraja N Raghu, Chandrashekar H Sankhe, Runali Pai, Kanthilatha Tender, Tenzin Mathew, Mary Aroor, Annayya Shetty, Ashok K Adiga, Shalini Devi, Vasudha Muttigi, Manjunatha S Upadhya, Dinesh Theranostics Research Paper Diabetic retinopathy (DR) is associated with retinal neovascularization, hard exudates, inflammation, oxidative stress and cell death, leading to vision loss. Anti-vascular endothelial growth factor (Anti-VEGF) therapy through repeated intravitreal injections is an established treatment for reducing VEGF levels in the retina for inhibiting neovascularization and leakage of hard exudates to prevent vision loss. Although anti-VEGF therapy has several clinical benefits, its monthly injection potentially causes devastating ocular complications, including trauma, intraocular hemorrhage, retinal detachment, endophthalmitis, etc. Methods: As mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) demonstrated safety in clinical studies, we have tested the efficacy of MSC-derived small EVs (MSC-sEVs) loaded anti-VEGF drug bevacizumab in a rat model of DR. Results: The study identified a clinically significant finding that sEV loaded with bevacizumab reduces the frequency of intravitreal injection required for treating diabetic retinopathy. The sustained effect is observed from the reduced levels of VEGF, exudates and leukostasis for more than two months following intravitreal injection of sEV loaded with bevacizumab, while bevacizumab alone could maintain reduced levels for about one month. Furthermore, retinal cell death was consistently lower in this period than only bevacizumab. Conclusion: This study provided significant evidence for the prolonged benefits of sEVs as a drug delivery system. Also, EV-mediated drug delivery systems could be considered for clinical application of retinal diseases as they maintain vitreous clarity in the light path due to their composition being similar to cells. Ivyspring International Publisher 2023-04-09 /pmc/articles/PMC10157735/ /pubmed/37153730 http://dx.doi.org/10.7150/thno.78426 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Reddy, Shivakumar K Ballal, Abhijna R Shailaja, S Seetharam, Raviraja N Raghu, Chandrashekar H Sankhe, Runali Pai, Kanthilatha Tender, Tenzin Mathew, Mary Aroor, Annayya Shetty, Ashok K Adiga, Shalini Devi, Vasudha Muttigi, Manjunatha S Upadhya, Dinesh Small extracellular vesicle-loaded bevacizumab reduces the frequency of intravitreal injection required for diabetic retinopathy |
title | Small extracellular vesicle-loaded bevacizumab reduces the frequency of intravitreal injection required for diabetic retinopathy |
title_full | Small extracellular vesicle-loaded bevacizumab reduces the frequency of intravitreal injection required for diabetic retinopathy |
title_fullStr | Small extracellular vesicle-loaded bevacizumab reduces the frequency of intravitreal injection required for diabetic retinopathy |
title_full_unstemmed | Small extracellular vesicle-loaded bevacizumab reduces the frequency of intravitreal injection required for diabetic retinopathy |
title_short | Small extracellular vesicle-loaded bevacizumab reduces the frequency of intravitreal injection required for diabetic retinopathy |
title_sort | small extracellular vesicle-loaded bevacizumab reduces the frequency of intravitreal injection required for diabetic retinopathy |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157735/ https://www.ncbi.nlm.nih.gov/pubmed/37153730 http://dx.doi.org/10.7150/thno.78426 |
work_keys_str_mv | AT reddyshivakumark smallextracellularvesicleloadedbevacizumabreducesthefrequencyofintravitrealinjectionrequiredfordiabeticretinopathy AT ballalabhijnar smallextracellularvesicleloadedbevacizumabreducesthefrequencyofintravitrealinjectionrequiredfordiabeticretinopathy AT shailajas smallextracellularvesicleloadedbevacizumabreducesthefrequencyofintravitrealinjectionrequiredfordiabeticretinopathy AT seetharamravirajan smallextracellularvesicleloadedbevacizumabreducesthefrequencyofintravitrealinjectionrequiredfordiabeticretinopathy AT raghuchandrashekarh smallextracellularvesicleloadedbevacizumabreducesthefrequencyofintravitrealinjectionrequiredfordiabeticretinopathy AT sankherunali smallextracellularvesicleloadedbevacizumabreducesthefrequencyofintravitrealinjectionrequiredfordiabeticretinopathy AT paikanthilatha smallextracellularvesicleloadedbevacizumabreducesthefrequencyofintravitrealinjectionrequiredfordiabeticretinopathy AT tendertenzin smallextracellularvesicleloadedbevacizumabreducesthefrequencyofintravitrealinjectionrequiredfordiabeticretinopathy AT mathewmary smallextracellularvesicleloadedbevacizumabreducesthefrequencyofintravitrealinjectionrequiredfordiabeticretinopathy AT aroorannayya smallextracellularvesicleloadedbevacizumabreducesthefrequencyofintravitrealinjectionrequiredfordiabeticretinopathy AT shettyashokk smallextracellularvesicleloadedbevacizumabreducesthefrequencyofintravitrealinjectionrequiredfordiabeticretinopathy AT adigashalini smallextracellularvesicleloadedbevacizumabreducesthefrequencyofintravitrealinjectionrequiredfordiabeticretinopathy AT devivasudha smallextracellularvesicleloadedbevacizumabreducesthefrequencyofintravitrealinjectionrequiredfordiabeticretinopathy AT muttigimanjunathas smallextracellularvesicleloadedbevacizumabreducesthefrequencyofintravitrealinjectionrequiredfordiabeticretinopathy AT upadhyadinesh smallextracellularvesicleloadedbevacizumabreducesthefrequencyofintravitrealinjectionrequiredfordiabeticretinopathy |