{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:29:15Z","timestamp":1790958555350,"version":"4.1.0"},"reference-count":64,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T00:00:00Z","timestamp":1662422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012415","name":"Biomedical Research Council","doi-asserted-by":"publisher","award":["SPF2014\/002"],"award-info":[{"award-number":["SPF2014\/002"]}],"id":[{"id":"10.13039\/501100012415","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012415","name":"Biomedical Research Council","doi-asserted-by":"publisher","award":["NMRC\/OFLCG\/004\/2018"],"award-info":[{"award-number":["NMRC\/OFLCG\/004\/2018"]}],"id":[{"id":"10.13039\/501100012415","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["SPF2014\/002"],"award-info":[{"award-number":["SPF2014\/002"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["NMRC\/OFLCG\/004\/2018"],"award-info":[{"award-number":["NMRC\/OFLCG\/004\/2018"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u201433% (20\/60) and wild-type (WT)\u20147% (1\/15), p &lt; 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 &lt; 0.05). Laser induced CNV in the CAG-HtrA1 Tg mice and showed increased leakage from CNV compared to WT mice (p &lt; 0.05). Finally, choroidal explants of the old CAG-HtrA1 Tg mice demonstrated an increased area of sprouting (p &lt; 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.<\/jats:p>","DOI":"10.3390\/ijms231810206","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T05:17:23Z","timestamp":1662441443000},"page":"10206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["HTRA1 Regulates Subclinical Inflammation and Activates Proangiogenic Response in the Retina and Choroid"],"prefix":"10.3390","volume":"23","author":[{"given":"Waseem","family":"Ahamed","sequence":"first","affiliation":[{"name":"Singapore National Eye Centre, Singapore Eye Research Institute, 11 Third Hospital Ave, Singapore 168751, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard Ming Chuan","family":"Yu","sequence":"additional","affiliation":[{"name":"Singapore National Eye Centre, Singapore Eye Research Institute, 11 Third Hospital Ave, Singapore 168751, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Pan","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology Division, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo 152-8902, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Iwata","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology Division, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo 152-8902, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6477-9784","authenticated-orcid":false,"given":"Veluchamy Amutha","family":"Barathi","sequence":"additional","affiliation":[{"name":"Singapore National Eye Centre, Singapore Eye Research Institute, 11 Third Hospital Ave, Singapore 168751, Singapore"},{"name":"Academic Clinical Program, Duke-NUS Medical School, National University of Singapore, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeo Sia","family":"Wey","sequence":"additional","affiliation":[{"name":"Singapore National Eye Centre, Singapore Eye Research Institute, 11 Third Hospital Ave, Singapore 168751, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2013-8379","authenticated-orcid":false,"given":"Sai Bo Bo","family":"Tun","sequence":"additional","affiliation":[{"name":"Singapore National Eye Centre, Singapore Eye Research Institute, 11 Third Hospital Ave, Singapore 168751, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beiying","family":"Qiu","sequence":"additional","affiliation":[{"name":"Singapore National Eye Centre, Singapore Eye Research Institute, 11 Third Hospital Ave, Singapore 168751, Singapore"},{"name":"Academic Clinical Program, Duke-NUS Medical School, National University of Singapore, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Tan","sequence":"additional","affiliation":[{"name":"Singapore National Eye Centre, Singapore Eye Research Institute, 11 Third Hospital Ave, Singapore 168751, Singapore"},{"name":"Academic Clinical Program, Duke-NUS Medical School, National University of Singapore, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Singapore National Eye Centre, Singapore Eye Research Institute, 11 Third Hospital Ave, Singapore 168751, Singapore"},{"name":"Academic Clinical Program, Duke-NUS Medical School, National University of Singapore, Singapore 169857, Singapore"},{"name":"Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3358-3516","authenticated-orcid":false,"given":"Chui Ming Gemmy","family":"Cheung","sequence":"additional","affiliation":[{"name":"Singapore National Eye Centre, Singapore Eye Research Institute, 11 Third Hospital Ave, Singapore 168751, Singapore"},{"name":"Academic Clinical Program, Duke-NUS Medical School, National University of Singapore, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tien Yin","family":"Wong","sequence":"additional","affiliation":[{"name":"Singapore National Eye Centre, Singapore Eye Research Institute, 11 Third Hospital Ave, Singapore 168751, Singapore"},{"name":"Academic Clinical Program, Duke-NUS Medical School, National University of Singapore, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Yanagi","sequence":"additional","affiliation":[{"name":"Singapore National Eye Centre, Singapore Eye Research Institute, 11 Third Hospital Ave, Singapore 168751, Singapore"},{"name":"Academic Clinical Program, Duke-NUS Medical School, National University of Singapore, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","article-title":"Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis","volume":"2","author":"Wong","year":"2014","journal-title":"Lancet Glob. 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