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HTRA1 Regulates Subclinical Inflammation and Activates Proangiogenic Response in the Retina and Choroid

High-temperature requirement A1 (HtrA1) has been identified as a disease-susceptibility gene for age-related macular degeneration (AMD) including polypoidal choroidal neovasculopathy (PCV). We characterized the underlying phenotypic changes of transgenic (Tg) mice expressing ubiquitous CAG promoter...

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Autores principales: Ahamed, Waseem, Yu, Richard Ming Chuan, Pan, Yang, Iwata, Takeshi, Barathi, Veluchamy Amutha, Wey, Yeo Sia, Tun, Sai Bo Bo, Qiu, Beiying, Tan, Alison, Wang, Xiaomeng, Cheung, Chui Ming Gemmy, Wong, Tien Yin, Yanagi, Yasuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499640/
https://www.ncbi.nlm.nih.gov/pubmed/36142120
http://dx.doi.org/10.3390/ijms231810206
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author Ahamed, Waseem
Yu, Richard Ming Chuan
Pan, Yang
Iwata, Takeshi
Barathi, Veluchamy Amutha
Wey, Yeo Sia
Tun, Sai Bo Bo
Qiu, Beiying
Tan, Alison
Wang, Xiaomeng
Cheung, Chui Ming Gemmy
Wong, Tien Yin
Yanagi, Yasuo
author_facet Ahamed, Waseem
Yu, Richard Ming Chuan
Pan, Yang
Iwata, Takeshi
Barathi, Veluchamy Amutha
Wey, Yeo Sia
Tun, Sai Bo Bo
Qiu, Beiying
Tan, Alison
Wang, Xiaomeng
Cheung, Chui Ming Gemmy
Wong, Tien Yin
Yanagi, Yasuo
author_sort Ahamed, Waseem
collection PubMed
description High-temperature requirement A1 (HtrA1) has been identified as a disease-susceptibility gene for age-related macular degeneration (AMD) including polypoidal choroidal neovasculopathy (PCV). We characterized the underlying phenotypic changes of transgenic (Tg) mice expressing ubiquitous CAG promoter (CAG-HtrA1 Tg). In vivo imaging modalities and histopathology were performed to investigate the possible neovascularization, drusen formation, and infiltration of macrophages. Subretinal white material deposition and scattered white-yellowish retinal foci were detected on CFP [(Tg—33% (20/60) and wild-type (WT)—7% (1/15), p < 0.05]. In 40% (4/10) of the CAG-HtrA1 Tg retina, ICGA showed punctate hyperfluorescent spots. There was no leakage on FFA and OCTA failed to confirm vascular flow signals from the subretinal materials. Increased macrophages and RPE cell migrations were noted from histopathological sections. Monocyte subpopulations were increased in peripheral blood in the CAG-HtrA1 Tg mice (p < 0.05). Laser induced CNV in the CAG-HtrA1 Tg mice and showed increased leakage from CNV compared to WT mice (p < 0.05). Finally, choroidal explants of the old CAG-HtrA1 Tg mice demonstrated an increased area of sprouting (p < 0.05). Signs of subclinical inflammation was observed in CAG-HtrA1 Tg mice. Such subclinical inflammation may have resulted in increased RPE cell activation and angiogenic potential.
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spelling pubmed-94996402022-09-23 HTRA1 Regulates Subclinical Inflammation and Activates Proangiogenic Response in the Retina and Choroid Ahamed, Waseem Yu, Richard Ming Chuan Pan, Yang Iwata, Takeshi Barathi, Veluchamy Amutha Wey, Yeo Sia Tun, Sai Bo Bo Qiu, Beiying Tan, Alison Wang, Xiaomeng Cheung, Chui Ming Gemmy Wong, Tien Yin Yanagi, Yasuo Int J Mol Sci Article High-temperature requirement A1 (HtrA1) has been identified as a disease-susceptibility gene for age-related macular degeneration (AMD) including polypoidal choroidal neovasculopathy (PCV). We characterized the underlying phenotypic changes of transgenic (Tg) mice expressing ubiquitous CAG promoter (CAG-HtrA1 Tg). In vivo imaging modalities and histopathology were performed to investigate the possible neovascularization, drusen formation, and infiltration of macrophages. Subretinal white material deposition and scattered white-yellowish retinal foci were detected on CFP [(Tg—33% (20/60) and wild-type (WT)—7% (1/15), p < 0.05]. In 40% (4/10) of the CAG-HtrA1 Tg retina, ICGA showed punctate hyperfluorescent spots. There was no leakage on FFA and OCTA failed to confirm vascular flow signals from the subretinal materials. Increased macrophages and RPE cell migrations were noted from histopathological sections. Monocyte subpopulations were increased in peripheral blood in the CAG-HtrA1 Tg mice (p < 0.05). Laser induced CNV in the CAG-HtrA1 Tg mice and showed increased leakage from CNV compared to WT mice (p < 0.05). Finally, choroidal explants of the old CAG-HtrA1 Tg mice demonstrated an increased area of sprouting (p < 0.05). Signs of subclinical inflammation was observed in CAG-HtrA1 Tg mice. Such subclinical inflammation may have resulted in increased RPE cell activation and angiogenic potential. MDPI 2022-09-06 /pmc/articles/PMC9499640/ /pubmed/36142120 http://dx.doi.org/10.3390/ijms231810206 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ahamed, Waseem
Yu, Richard Ming Chuan
Pan, Yang
Iwata, Takeshi
Barathi, Veluchamy Amutha
Wey, Yeo Sia
Tun, Sai Bo Bo
Qiu, Beiying
Tan, Alison
Wang, Xiaomeng
Cheung, Chui Ming Gemmy
Wong, Tien Yin
Yanagi, Yasuo
HTRA1 Regulates Subclinical Inflammation and Activates Proangiogenic Response in the Retina and Choroid
title HTRA1 Regulates Subclinical Inflammation and Activates Proangiogenic Response in the Retina and Choroid
title_full HTRA1 Regulates Subclinical Inflammation and Activates Proangiogenic Response in the Retina and Choroid
title_fullStr HTRA1 Regulates Subclinical Inflammation and Activates Proangiogenic Response in the Retina and Choroid
title_full_unstemmed HTRA1 Regulates Subclinical Inflammation and Activates Proangiogenic Response in the Retina and Choroid
title_short HTRA1 Regulates Subclinical Inflammation and Activates Proangiogenic Response in the Retina and Choroid
title_sort htra1 regulates subclinical inflammation and activates proangiogenic response in the retina and choroid
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499640/
https://www.ncbi.nlm.nih.gov/pubmed/36142120
http://dx.doi.org/10.3390/ijms231810206
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