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Expression of purinergic receptors on microglia in the animal model of choroidal neovascularisation

To investigate the effect of P2 receptor on microglia and its inhibitor PPADS on choroidal neovascularization. Forty CX3CR1(GFP/+) mice were randomly divided into 8 groups. In addition to the normal group, the rest of groups were receiving laser treatment. The retina and choroid from the second, thi...

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Autores principales: Li, Lu, Liu, Juejun, Xu, Amin, Heiduschka, Peter, Eter, Nicole, Chen, Changzheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196182/
https://www.ncbi.nlm.nih.gov/pubmed/34117330
http://dx.doi.org/10.1038/s41598-021-91989-4
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author Li, Lu
Liu, Juejun
Xu, Amin
Heiduschka, Peter
Eter, Nicole
Chen, Changzheng
author_facet Li, Lu
Liu, Juejun
Xu, Amin
Heiduschka, Peter
Eter, Nicole
Chen, Changzheng
author_sort Li, Lu
collection PubMed
description To investigate the effect of P2 receptor on microglia and its inhibitor PPADS on choroidal neovascularization. Forty CX3CR1(GFP/+) mice were randomly divided into 8 groups. In addition to the normal group, the rest of groups were receiving laser treatment. The retina and choroid from the second, third, fourth and fifth group of mice were taken in the 1, 4, 7, 14 days after laser treatment. The mice in the sixth and seventh group received intravitreal injection of 2 µl PPADS or PBS respectively immediately after laser treatment. The mice in the eighth group received topical application of PPADS once per day of three days. The mice in sixth, seventh and eighth group received AF and FFA examination on the fourth day after laser treatment. Immunofluorescence histochemical staining and real-time quantitative PCR were used to evaluate P2 expression and its effect on choroidal neovascularization. After laser treatment, activated microglia can express P2 receptors (P2X4, P2X7, P2Y2 and P2Y12). The expression of P2 increased on the first day after laser damage, peaked on the fourth day (t(P2X4) = 6.05, t(P2X7) = 2.95, t(P2Y2) = 3.67, t(P2Y12) = 5.98, all P < 0.01), and then decreased. After PPADS inhibition, compared with the PBS injection group, the mRNA of P2X4, P2X7, P2Y2 and P2Y12 were decreased significantly in the PPADS injection group (t(P2X4) = 5.54, t(P2X7) = 9.82, t(P2Y2) = 3.86, t(P2Y12) = 7.91, all P < 0.01) and the PPADS topical application group (t(P2X4) = 3.24, t(P2X7) = 5.89, t(P2Y2) = 6.75, t(P2Y12) = 4.97, all P < 0.01). Compared with the PBS injection group, not only the activity of microglia cells but also the leakage of CNV decreased significantly (P < 0.01) in the PPADS injection group and the PPADS topical application group. But between two PPADS groups, the leakage of CNV had no difference (P = 0.864). After laser induced CNV, activated microglia can express P2 receptors. The P2 receptor inhibitor, PPADS, can significantly affect the function of microglia and inhibit the formation of choroidal neovascularization.
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spelling pubmed-81961822021-06-15 Expression of purinergic receptors on microglia in the animal model of choroidal neovascularisation Li, Lu Liu, Juejun Xu, Amin Heiduschka, Peter Eter, Nicole Chen, Changzheng Sci Rep Article To investigate the effect of P2 receptor on microglia and its inhibitor PPADS on choroidal neovascularization. Forty CX3CR1(GFP/+) mice were randomly divided into 8 groups. In addition to the normal group, the rest of groups were receiving laser treatment. The retina and choroid from the second, third, fourth and fifth group of mice were taken in the 1, 4, 7, 14 days after laser treatment. The mice in the sixth and seventh group received intravitreal injection of 2 µl PPADS or PBS respectively immediately after laser treatment. The mice in the eighth group received topical application of PPADS once per day of three days. The mice in sixth, seventh and eighth group received AF and FFA examination on the fourth day after laser treatment. Immunofluorescence histochemical staining and real-time quantitative PCR were used to evaluate P2 expression and its effect on choroidal neovascularization. After laser treatment, activated microglia can express P2 receptors (P2X4, P2X7, P2Y2 and P2Y12). The expression of P2 increased on the first day after laser damage, peaked on the fourth day (t(P2X4) = 6.05, t(P2X7) = 2.95, t(P2Y2) = 3.67, t(P2Y12) = 5.98, all P < 0.01), and then decreased. After PPADS inhibition, compared with the PBS injection group, the mRNA of P2X4, P2X7, P2Y2 and P2Y12 were decreased significantly in the PPADS injection group (t(P2X4) = 5.54, t(P2X7) = 9.82, t(P2Y2) = 3.86, t(P2Y12) = 7.91, all P < 0.01) and the PPADS topical application group (t(P2X4) = 3.24, t(P2X7) = 5.89, t(P2Y2) = 6.75, t(P2Y12) = 4.97, all P < 0.01). Compared with the PBS injection group, not only the activity of microglia cells but also the leakage of CNV decreased significantly (P < 0.01) in the PPADS injection group and the PPADS topical application group. But between two PPADS groups, the leakage of CNV had no difference (P = 0.864). After laser induced CNV, activated microglia can express P2 receptors. The P2 receptor inhibitor, PPADS, can significantly affect the function of microglia and inhibit the formation of choroidal neovascularization. Nature Publishing Group UK 2021-06-11 /pmc/articles/PMC8196182/ /pubmed/34117330 http://dx.doi.org/10.1038/s41598-021-91989-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Li, Lu
Liu, Juejun
Xu, Amin
Heiduschka, Peter
Eter, Nicole
Chen, Changzheng
Expression of purinergic receptors on microglia in the animal model of choroidal neovascularisation
title Expression of purinergic receptors on microglia in the animal model of choroidal neovascularisation
title_full Expression of purinergic receptors on microglia in the animal model of choroidal neovascularisation
title_fullStr Expression of purinergic receptors on microglia in the animal model of choroidal neovascularisation
title_full_unstemmed Expression of purinergic receptors on microglia in the animal model of choroidal neovascularisation
title_short Expression of purinergic receptors on microglia in the animal model of choroidal neovascularisation
title_sort expression of purinergic receptors on microglia in the animal model of choroidal neovascularisation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196182/
https://www.ncbi.nlm.nih.gov/pubmed/34117330
http://dx.doi.org/10.1038/s41598-021-91989-4
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