TY - JOUR
T1 - Angiopoietin-1 Is Required for Vortex Vein and Choriocapillaris Development in Mice
AU - Liu, Pan
AU - Lavine, Jeremy A.
AU - Fawzi, Amani
AU - Quaggin, Susan E.
AU - Thomson, Benjamin R.
N1 - Funding Information:
B.R. Thomson and P. Liu have applied for patents related to targeting of the angiopoietin-TEK pathway in choroidal diseases. Additionally, B.R. Thomson receives research funding from Bayer. S.E. Quaggin holds patents related to therapeutic targeting of the ANGPT-TEK pathway in ocular hypertension, glaucoma and vascular diseases and owns stock in Mannin Research. S.E. Quaggin also receives consulting fees from AstraZeneca, Janssen, the Lowy Medical Research Foundation, Novartis, Pfizer, Janssen, UNITY and Roche/Genentech. AAF receives grant support from Boehringer Ingelheim, as well as consulting fees from Regeneron, Roche/Genentech and Boehringer Ingelheim. The other authors declare no competing interests.
Funding Information:
This work was supported by R01 EY032609 (to B.R. Thomson), R01 EY025799 (to S.E. Quaggin) and R01 EY030121 (to A. Fawzi). This work was generously supported by the donors of the Brightfocus Foundation through new investigator grant in macular degeneration research M2021018N to B.R. Thomson. In addition, funding for this research was supported by the Global Ophthalmology Awards Program (GOAP), a Bayer-sponsored initiative committed to supporting ophthalmic research across the world. JAL was supported by NIH grant K08 EY030923, the Research to Prevent Blindness Sybil B. Harrington Career Development Award for Macular Degeneration and a Brightfocus foundation new investigator grant in macular degeneration research. Imaging was performed at the Center for Advanced Microscopy of the Feinberg School of Medicine supported by NCI CCSG P30 CA60553. Work was also supported by a Research to Prevent Blindness Unrestricted Award to the Northwestern University Department of Ophthalmology and the NIH George M. O’Brien kidney core grant P30 DK114857 awarded to the Section of Nephrology and Hypertension.
Funding Information:
This work was supported by R01 EY032609 (to B.R. Thomson), R01 EY025799 (to S.E. Quaggin) and R01 EY030121 (to A. Fawzi). This work was generously supported by the donors of the Brightfocus Foundation through new investigator grant in macular degeneration research M2021018N to B.R. Thomson. In addition, funding for this research was supported by the Global Ophthalmology Awards Program (GOAP), a Bayer-sponsored initiative committed to supporting ophthalmic research across the world. JAL was supported by NIH grant K08 EY030923, the Research to Prevent Blindness Sybil B. Harrington Career Development Award for Macular Degeneration and a Brightfocus foundation new investigator grant in macular degeneration research. Imaging was performed at the Center for Advanced Microscopy of the Feinberg School of Medicine supported by NCI CCSG P30 CA60553. Work was also supported by a Research to Prevent Blindness Unrestricted Award to the Northwestern University Department of Ophthalmology and the NIH George M. O’Brien kidney core grant P30 DK114857 awarded to the Section of Nephrology and Hypertension.
Publisher Copyright:
© 2022 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2022/11/1
Y1 - 2022/11/1
N2 - Background: The choroidal vasculature, including the choriocapillaris and vortex veins, is essential for providing nutrients to the metabolically demanding photoreceptors and retinal pigment epithelium. Choroidal vascular dysfunction leads to vision loss and is associated with age-related macular degeneration and the poorly understood pachychoroid diseases including central serous chorioretinopathy and polypoidal choroidal vasculopathy that are characterized by formation of dilated pachyvessels throughout the choroid. Methods: Using neural crest-specific Angpt1 knockout mice, we show that Angiopoietin 1, a ligand of the endothelial receptor TEK (also known as Tie2) is essential for choriocapillaris development and vortex vein patterning. Results: Lacking choroidal ANGPT1, neural crest-specific Angpt1 knockout eyes exhibited marked choriocapillaris attenuation and 50% reduction in number of vortex veins, with only 2 vortex veins present in the majority of eyes. Shortly after birth, dilated choroidal vessels resembling human pachyvessels were observed extending from the remaining vortex veins and displacing the choriocapillaris, leading to retinal pigment epithelium dysfunction and subretinal neovascularization similar to that seen in pachychoroid disease. Conclusions: Together, these findings identify a new role for ANGPT1 in ocular vascular development and demonstrate a clear link between vortex vein dysfunction, pachyvessel formation, and disease.
AB - Background: The choroidal vasculature, including the choriocapillaris and vortex veins, is essential for providing nutrients to the metabolically demanding photoreceptors and retinal pigment epithelium. Choroidal vascular dysfunction leads to vision loss and is associated with age-related macular degeneration and the poorly understood pachychoroid diseases including central serous chorioretinopathy and polypoidal choroidal vasculopathy that are characterized by formation of dilated pachyvessels throughout the choroid. Methods: Using neural crest-specific Angpt1 knockout mice, we show that Angiopoietin 1, a ligand of the endothelial receptor TEK (also known as Tie2) is essential for choriocapillaris development and vortex vein patterning. Results: Lacking choroidal ANGPT1, neural crest-specific Angpt1 knockout eyes exhibited marked choriocapillaris attenuation and 50% reduction in number of vortex veins, with only 2 vortex veins present in the majority of eyes. Shortly after birth, dilated choroidal vessels resembling human pachyvessels were observed extending from the remaining vortex veins and displacing the choriocapillaris, leading to retinal pigment epithelium dysfunction and subretinal neovascularization similar to that seen in pachychoroid disease. Conclusions: Together, these findings identify a new role for ANGPT1 in ocular vascular development and demonstrate a clear link between vortex vein dysfunction, pachyvessel formation, and disease.
KW - angiopoietin
KW - choriocapillaris
KW - pachychoroid
KW - polypoidal choroidal vasculopathy
KW - vortex vein
UR - http://www.scopus.com/inward/record.url?scp=85140856512&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85140856512&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.122.318151
DO - 10.1161/ATVBAHA.122.318151
M3 - Article
C2 - 36172864
AN - SCOPUS:85140856512
SN - 1079-5642
VL - 42
SP - 1413
EP - 1427
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 11
ER -