Microphysiological Neurovascular Barriers to Model the Inner Retinal Microvasculature

Blood-neural barriers regulate nutrient supply to neuronal tissues and prevent neurotoxicity. In particular, the inner blood-retinal barrier (iBRB) and blood–brain barrier (BBB) share common origins in development, and similar morphology and function in adult tissue, while barrier breakdow...

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Main Authors: Maurissen, Thomas L., Pavlou, Georgios, Bichsel, Colette, Villaseñor, Roberto, Kamm, Roger D., Ragelle, Héloïse
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Published: MDPI AG 2022
Online Access:https://hdl.handle.net/1721.1/140289
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author Maurissen, Thomas L.
Pavlou, Georgios
Bichsel, Colette
Villaseñor, Roberto
Kamm, Roger D.
Ragelle, Héloïse
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Maurissen, Thomas L.
Pavlou, Georgios
Bichsel, Colette
Villaseñor, Roberto
Kamm, Roger D.
Ragelle, Héloïse
author_sort Maurissen, Thomas L.
collection MIT
description Blood-neural barriers regulate nutrient supply to neuronal tissues and prevent neurotoxicity. In particular, the inner blood-retinal barrier (iBRB) and blood–brain barrier (BBB) share common origins in development, and similar morphology and function in adult tissue, while barrier breakdown and leakage of neurotoxic molecules can be accompanied by neurodegeneration. Therefore, pre-clinical research requires human in vitro models that elucidate pathophysiological mechanisms and support drug discovery, to add to animal in vivo modeling that poorly predict patient responses. Advanced cellular models such as microphysiological systems (MPS) recapitulate tissue organization and function in many organ-specific contexts, providing physiological relevance, potential for customization to different population groups, and scalability for drug screening purposes. While human-based MPS have been developed for tissues such as lung, gut, brain and tumors, few comprehensive models exist for ocular tissues and iBRB modeling. Recent BBB in vitro models using human cells of the neurovascular unit (NVU) showed physiological morphology and permeability values, and reproduced brain neurological disorder phenotypes that could be applicable to modeling the iBRB. Here, we describe similarities between iBRB and BBB properties, compare existing neurovascular barrier models, propose leverage of MPS-based strategies to develop new iBRB models, and explore potentials to personalize cellular inputs and improve pre-clinical testing.
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spelling mit-1721.1/1402892024-06-07T17:37:35Z Microphysiological Neurovascular Barriers to Model the Inner Retinal Microvasculature Maurissen, Thomas L. Pavlou, Georgios Bichsel, Colette Villaseñor, Roberto Kamm, Roger D. Ragelle, Héloïse Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Blood-neural barriers regulate nutrient supply to neuronal tissues and prevent neurotoxicity. In particular, the inner blood-retinal barrier (iBRB) and blood–brain barrier (BBB) share common origins in development, and similar morphology and function in adult tissue, while barrier breakdown and leakage of neurotoxic molecules can be accompanied by neurodegeneration. Therefore, pre-clinical research requires human in vitro models that elucidate pathophysiological mechanisms and support drug discovery, to add to animal in vivo modeling that poorly predict patient responses. Advanced cellular models such as microphysiological systems (MPS) recapitulate tissue organization and function in many organ-specific contexts, providing physiological relevance, potential for customization to different population groups, and scalability for drug screening purposes. While human-based MPS have been developed for tissues such as lung, gut, brain and tumors, few comprehensive models exist for ocular tissues and iBRB modeling. Recent BBB in vitro models using human cells of the neurovascular unit (NVU) showed physiological morphology and permeability values, and reproduced brain neurological disorder phenotypes that could be applicable to modeling the iBRB. Here, we describe similarities between iBRB and BBB properties, compare existing neurovascular barrier models, propose leverage of MPS-based strategies to develop new iBRB models, and explore potentials to personalize cellular inputs and improve pre-clinical testing. 2022-02-11T17:22:00Z 2022-02-11T17:22:00Z 2022-01-24 2022-02-11T14:46:24Z Article http://purl.org/eprint/type/JournalArticle 2075-4426 https://hdl.handle.net/1721.1/140289 Maurissen TL, Pavlou G, Bichsel C, Villaseñor R, Kamm RD, Ragelle H. Microphysiological Neurovascular Barriers to Model the Inner Retinal Microvasculature. Journal of Personalized Medicine. 2022; 12(2):148 10.3390/jpm12020148 Journal of Personalized Medicine Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ application/pdf MDPI AG Multidisciplinary Digital Publishing Institute
spellingShingle Maurissen, Thomas L.
Pavlou, Georgios
Bichsel, Colette
Villaseñor, Roberto
Kamm, Roger D.
Ragelle, Héloïse
Microphysiological Neurovascular Barriers to Model the Inner Retinal Microvasculature
title Microphysiological Neurovascular Barriers to Model the Inner Retinal Microvasculature
title_full Microphysiological Neurovascular Barriers to Model the Inner Retinal Microvasculature
title_fullStr Microphysiological Neurovascular Barriers to Model the Inner Retinal Microvasculature
title_full_unstemmed Microphysiological Neurovascular Barriers to Model the Inner Retinal Microvasculature
title_short Microphysiological Neurovascular Barriers to Model the Inner Retinal Microvasculature
title_sort microphysiological neurovascular barriers to model the inner retinal microvasculature
url https://hdl.handle.net/1721.1/140289
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