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Targeted Thrombospondin-1 Expression in Ocular Vascular Development and Neovascularization

Tight regulation of positive and negative regulators of angiogenesis is essential, particularly in the eye where their dysregulation can lead to vision loss. Thrombospondin-1 (TSP1) is a matricellular protein that negatively regulates angiogenesis and inflammation in the eye. It aids ocular vascular...

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Autores principales: Sorenson, Christine M., Wang, Shoujian, Darjatmoko, Soesiawati R., Gurel, Zafer, Liu, Bo, Sheibani, Nader
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097095/
https://www.ncbi.nlm.nih.gov/pubmed/33968943
http://dx.doi.org/10.3389/fcell.2021.671989
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author Sorenson, Christine M.
Wang, Shoujian
Darjatmoko, Soesiawati R.
Gurel, Zafer
Liu, Bo
Sheibani, Nader
author_facet Sorenson, Christine M.
Wang, Shoujian
Darjatmoko, Soesiawati R.
Gurel, Zafer
Liu, Bo
Sheibani, Nader
author_sort Sorenson, Christine M.
collection PubMed
description Tight regulation of positive and negative regulators of angiogenesis is essential, particularly in the eye where their dysregulation can lead to vision loss. Thrombospondin-1 (TSP1) is a matricellular protein that negatively regulates angiogenesis and inflammation in the eye. It aids ocular vascular homeostasis such that its loss contributes to increased retinal vascular density and pathologic ocular neovascularization. Our previous studies demonstrated that mice globally lacking TSP1 expression had increased retinal vascular density, decreased hyperoxia-induced retinal vessel loss, and increased choroidal neovascularization. Here we determined the impact to the ocular vasculature of endothelial cell, pericyte, or astrocyte loss of TSP1 expression. Only lack of TSP1 expression in endothelial cells was sufficient to increase choroidal neovascularization with mice lacking expression in pericytes or astrocytes not demonstrating a significant impact. Although the global TSP1 knockout mice demonstrated increased retinal vascular density, individual cell type loss of TSP1 resulted in decreased retinal endothelial cell numbers before and/or after vascular maturation in a cell type specific fashion. Retinas from mice lacking TSP1 expression in endothelial cells, pericytes or astrocytes were not protected from retinal vessel regression in response to hyperoxia as we previously observed in the global knockout. Thus, modulation of TSP1 expression in individual cell types demonstrates a response that is unique to the role TSP1 plays in that cell type of interest, and their coordinated activity is critical for vision.
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spelling pubmed-80970952021-05-06 Targeted Thrombospondin-1 Expression in Ocular Vascular Development and Neovascularization Sorenson, Christine M. Wang, Shoujian Darjatmoko, Soesiawati R. Gurel, Zafer Liu, Bo Sheibani, Nader Front Cell Dev Biol Cell and Developmental Biology Tight regulation of positive and negative regulators of angiogenesis is essential, particularly in the eye where their dysregulation can lead to vision loss. Thrombospondin-1 (TSP1) is a matricellular protein that negatively regulates angiogenesis and inflammation in the eye. It aids ocular vascular homeostasis such that its loss contributes to increased retinal vascular density and pathologic ocular neovascularization. Our previous studies demonstrated that mice globally lacking TSP1 expression had increased retinal vascular density, decreased hyperoxia-induced retinal vessel loss, and increased choroidal neovascularization. Here we determined the impact to the ocular vasculature of endothelial cell, pericyte, or astrocyte loss of TSP1 expression. Only lack of TSP1 expression in endothelial cells was sufficient to increase choroidal neovascularization with mice lacking expression in pericytes or astrocytes not demonstrating a significant impact. Although the global TSP1 knockout mice demonstrated increased retinal vascular density, individual cell type loss of TSP1 resulted in decreased retinal endothelial cell numbers before and/or after vascular maturation in a cell type specific fashion. Retinas from mice lacking TSP1 expression in endothelial cells, pericytes or astrocytes were not protected from retinal vessel regression in response to hyperoxia as we previously observed in the global knockout. Thus, modulation of TSP1 expression in individual cell types demonstrates a response that is unique to the role TSP1 plays in that cell type of interest, and their coordinated activity is critical for vision. Frontiers Media S.A. 2021-04-21 /pmc/articles/PMC8097095/ /pubmed/33968943 http://dx.doi.org/10.3389/fcell.2021.671989 Text en Copyright © 2021 Sorenson, Wang, Darjatmoko, Gurel, Liu and Sheibani. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Sorenson, Christine M.
Wang, Shoujian
Darjatmoko, Soesiawati R.
Gurel, Zafer
Liu, Bo
Sheibani, Nader
Targeted Thrombospondin-1 Expression in Ocular Vascular Development and Neovascularization
title Targeted Thrombospondin-1 Expression in Ocular Vascular Development and Neovascularization
title_full Targeted Thrombospondin-1 Expression in Ocular Vascular Development and Neovascularization
title_fullStr Targeted Thrombospondin-1 Expression in Ocular Vascular Development and Neovascularization
title_full_unstemmed Targeted Thrombospondin-1 Expression in Ocular Vascular Development and Neovascularization
title_short Targeted Thrombospondin-1 Expression in Ocular Vascular Development and Neovascularization
title_sort targeted thrombospondin-1 expression in ocular vascular development and neovascularization
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097095/
https://www.ncbi.nlm.nih.gov/pubmed/33968943
http://dx.doi.org/10.3389/fcell.2021.671989
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