ANGPTL7, a therapeutic target for increased intraocular pressure and glaucoma

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

ANGPTL7, a therapeutic target for increased intraocular pressure and glaucoma. / Praveen, Kavita; Patel, Gaurang C.; Gurski, Lauren; Ayer, Ariane H.; Persaud, Trikaladarshi; Still, Matthew D.; Miloscio, Lawrence; Van Zyl, Tavé; Di Gioia, Silvio Alessandro; Brumpton, Ben; Krebs, Kristi; Åsvold, Bjørn Olav; Chen, Esteban; Chavali, Venkata R. M.; Fury, Wen; Gudiseva, Harini V.; Hyde, Sarah; Jorgenson, Eric; Lefebvre, Stephanie; Li, Dadong; Li, Alexander; Mclninch, James; Patel, Brijeshkumar; Rabinowitz, Jeremy S.; Salowe, Rebecca; Schurmann, Claudia; Seidelin, Anne-Sofie; Stahl, Eli; Sun, Dylan; Teslovich, Tanya M.; Tybjærg-Hansen, Anne; Willer, Cristen; Waldron, Scott; Walley, Sabrina; Yang, Hua; Zaveri, Sarthak; Hu, Ying; Hveem, Kristian; Melander, Olle; Milani, Lili; Stender, Stefan; O'Brien, Joan M.; Jones, Marcus B.; Abecasis, Gonçalo R.; Cantor, Michael N.; Weyne, Jonathan; Karalis, Katia; Economides, Aris; Della Gatta, Giusy; Ferreira, Manuel A.; Yancopoulos, George D.; Baras, Aris; Romano, Carmelo; Coppola, Giovanni; Regeneron Genetics Center; GHS-RGC DiscovEHR Collaboration; Estonian Biobank Research Team.

I: Communications Biology , Bind 5, 1051, 2022.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Praveen, K, Patel, GC, Gurski, L, Ayer, AH, Persaud, T, Still, MD, Miloscio, L, Van Zyl, T, Di Gioia, SA, Brumpton, B, Krebs, K, Åsvold, BO, Chen, E, Chavali, VRM, Fury, W, Gudiseva, HV, Hyde, S, Jorgenson, E, Lefebvre, S, Li, D, Li, A, Mclninch, J, Patel, B, Rabinowitz, JS, Salowe, R, Schurmann, C, Seidelin, A-S, Stahl, E, Sun, D, Teslovich, TM, Tybjærg-Hansen, A, Willer, C, Waldron, S, Walley, S, Yang, H, Zaveri, S, Hu, Y, Hveem, K, Melander, O, Milani, L, Stender, S, O'Brien, JM, Jones, MB, Abecasis, GR, Cantor, MN, Weyne, J, Karalis, K, Economides, A, Della Gatta, G, Ferreira, MA, Yancopoulos, GD, Baras, A, Romano, C, Coppola, G, Regeneron Genetics Center, GHS-RGC DiscovEHR Collaboration & Estonian Biobank Research Team 2022, 'ANGPTL7, a therapeutic target for increased intraocular pressure and glaucoma', Communications Biology , bind 5, 1051. https://doi.org/10.1038/s42003-022-03932-6

APA

Praveen, K., Patel, G. C., Gurski, L., Ayer, A. H., Persaud, T., Still, M. D., Miloscio, L., Van Zyl, T., Di Gioia, S. A., Brumpton, B., Krebs, K., Åsvold, B. O., Chen, E., Chavali, V. R. M., Fury, W., Gudiseva, H. V., Hyde, S., Jorgenson, E., Lefebvre, S., ... Estonian Biobank Research Team (2022). ANGPTL7, a therapeutic target for increased intraocular pressure and glaucoma. Communications Biology , 5, [1051]. https://doi.org/10.1038/s42003-022-03932-6

Vancouver

Praveen K, Patel GC, Gurski L, Ayer AH, Persaud T, Still MD o.a. ANGPTL7, a therapeutic target for increased intraocular pressure and glaucoma. Communications Biology . 2022;5. 1051. https://doi.org/10.1038/s42003-022-03932-6

Author

Praveen, Kavita ; Patel, Gaurang C. ; Gurski, Lauren ; Ayer, Ariane H. ; Persaud, Trikaladarshi ; Still, Matthew D. ; Miloscio, Lawrence ; Van Zyl, Tavé ; Di Gioia, Silvio Alessandro ; Brumpton, Ben ; Krebs, Kristi ; Åsvold, Bjørn Olav ; Chen, Esteban ; Chavali, Venkata R. M. ; Fury, Wen ; Gudiseva, Harini V. ; Hyde, Sarah ; Jorgenson, Eric ; Lefebvre, Stephanie ; Li, Dadong ; Li, Alexander ; Mclninch, James ; Patel, Brijeshkumar ; Rabinowitz, Jeremy S. ; Salowe, Rebecca ; Schurmann, Claudia ; Seidelin, Anne-Sofie ; Stahl, Eli ; Sun, Dylan ; Teslovich, Tanya M. ; Tybjærg-Hansen, Anne ; Willer, Cristen ; Waldron, Scott ; Walley, Sabrina ; Yang, Hua ; Zaveri, Sarthak ; Hu, Ying ; Hveem, Kristian ; Melander, Olle ; Milani, Lili ; Stender, Stefan ; O'Brien, Joan M. ; Jones, Marcus B. ; Abecasis, Gonçalo R. ; Cantor, Michael N. ; Weyne, Jonathan ; Karalis, Katia ; Economides, Aris ; Della Gatta, Giusy ; Ferreira, Manuel A. ; Yancopoulos, George D. ; Baras, Aris ; Romano, Carmelo ; Coppola, Giovanni ; Regeneron Genetics Center ; GHS-RGC DiscovEHR Collaboration ; Estonian Biobank Research Team. / ANGPTL7, a therapeutic target for increased intraocular pressure and glaucoma. I: Communications Biology . 2022 ; Bind 5.

Bibtex

@article{fa70bc4be5a5476180b1c0f993b851f8,

title = "ANGPTL7, a therapeutic target for increased intraocular pressure and glaucoma",

abstract = "Glaucoma is a leading cause of blindness. Current glaucoma medications work by lowering intraocular pressure (IOP), a risk factor for glaucoma, but most treatments do not directly target the pathological changes leading to increased IOP, which can manifest as medication resistance as disease progresses. To identify physiological modulators of IOP, we performed genome- and exome-wide association analysis in >129,000 individuals with IOP measurements and extended these findings to an analysis of glaucoma risk. We report the identification and functional characterization of rare coding variants (including loss-of-function variants) in ANGPTL7 associated with reduction in IOP and glaucoma protection. We validated the human genetics findings in mice by establishing that Angptl7 knockout mice have lower (~2 mmHg) basal IOP compared to wild-type, with a trend towards lower IOP also in heterozygotes. Conversely, increasing murine Angptl7 levels via injection into mouse eyes increases the IOP. We also show that acute Angptl7 silencing in adult mice lowers the IOP (~2-4 mmHg), reproducing the observations in knockout mice. Collectively, our data suggest that ANGPTL7 is important for IOP homeostasis and is amenable to therapeutic modulation to help maintain a healthy IOP that can prevent onset or slow the progression of glaucoma.",

author = "Kavita Praveen and Patel, {Gaurang C.} and Lauren Gurski and Ayer, {Ariane H.} and Trikaladarshi Persaud and Still, {Matthew D.} and Lawrence Miloscio and {Van Zyl}, Tav{\'e} and {Di Gioia}, {Silvio Alessandro} and Ben Brumpton and Kristi Krebs and {\AA}svold, {Bj{\o}rn Olav} and Esteban Chen and Chavali, {Venkata R. M.} and Wen Fury and Gudiseva, {Harini V.} and Sarah Hyde and Eric Jorgenson and Stephanie Lefebvre and Dadong Li and Alexander Li and James Mclninch and Brijeshkumar Patel and Rabinowitz, {Jeremy S.} and Rebecca Salowe and Claudia Schurmann and Anne-Sofie Seidelin and Eli Stahl and Dylan Sun and Teslovich, {Tanya M.} and Anne Tybj{\ae}rg-Hansen and Cristen Willer and Scott Waldron and Sabrina Walley and Hua Yang and Sarthak Zaveri and Ying Hu and Kristian Hveem and Olle Melander and Lili Milani and Stefan Stender and O'Brien, {Joan M.} and Jones, {Marcus B.} and Abecasis, {Gon{\c c}alo R.} and Cantor, {Michael N.} and Jonathan Weyne and Katia Karalis and Aris Economides and {Della Gatta}, Giusy and Ferreira, {Manuel A.} and Yancopoulos, {George D.} and Aris Baras and Carmelo Romano and Giovanni Coppola and {Regeneron Genetics Center} and {GHS-RGC DiscovEHR Collaboration} and {Estonian Biobank Research Team}",

note = "Publisher Copyright: {\textcopyright} 2022. The Author(s).",

year = "2022",

doi = "10.1038/s42003-022-03932-6",

language = "English",

volume = "5",

journal = "Communications Biology",

issn = "2399-3642",

publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - ANGPTL7, a therapeutic target for increased intraocular pressure and glaucoma

AU - Praveen, Kavita

AU - Patel, Gaurang C.

AU - Gurski, Lauren

AU - Ayer, Ariane H.

AU - Persaud, Trikaladarshi

AU - Still, Matthew D.

AU - Miloscio, Lawrence

AU - Van Zyl, Tavé

AU - Di Gioia, Silvio Alessandro

AU - Brumpton, Ben

AU - Krebs, Kristi

AU - Åsvold, Bjørn Olav

AU - Chen, Esteban

AU - Chavali, Venkata R. M.

AU - Fury, Wen

AU - Gudiseva, Harini V.

AU - Hyde, Sarah

AU - Jorgenson, Eric

AU - Lefebvre, Stephanie

AU - Li, Dadong

AU - Li, Alexander

AU - Mclninch, James

AU - Patel, Brijeshkumar

AU - Rabinowitz, Jeremy S.

AU - Salowe, Rebecca

AU - Schurmann, Claudia

AU - Seidelin, Anne-Sofie

AU - Stahl, Eli

AU - Sun, Dylan

AU - Teslovich, Tanya M.

AU - Tybjærg-Hansen, Anne

AU - Willer, Cristen

AU - Waldron, Scott

AU - Walley, Sabrina

AU - Yang, Hua

AU - Zaveri, Sarthak

AU - Hu, Ying

AU - Hveem, Kristian

AU - Melander, Olle

AU - Milani, Lili

AU - Stender, Stefan

AU - O'Brien, Joan M.

AU - Jones, Marcus B.

AU - Abecasis, Gonçalo R.

AU - Cantor, Michael N.

AU - Weyne, Jonathan

AU - Karalis, Katia

AU - Economides, Aris

AU - Della Gatta, Giusy

AU - Ferreira, Manuel A.

AU - Yancopoulos, George D.

AU - Baras, Aris

AU - Romano, Carmelo

AU - Coppola, Giovanni

AU - Regeneron Genetics Center

AU - GHS-RGC DiscovEHR Collaboration

AU - Estonian Biobank Research Team

PY - 2022

Y1 - 2022

N2 - Glaucoma is a leading cause of blindness. Current glaucoma medications work by lowering intraocular pressure (IOP), a risk factor for glaucoma, but most treatments do not directly target the pathological changes leading to increased IOP, which can manifest as medication resistance as disease progresses. To identify physiological modulators of IOP, we performed genome- and exome-wide association analysis in >129,000 individuals with IOP measurements and extended these findings to an analysis of glaucoma risk. We report the identification and functional characterization of rare coding variants (including loss-of-function variants) in ANGPTL7 associated with reduction in IOP and glaucoma protection. We validated the human genetics findings in mice by establishing that Angptl7 knockout mice have lower (~2 mmHg) basal IOP compared to wild-type, with a trend towards lower IOP also in heterozygotes. Conversely, increasing murine Angptl7 levels via injection into mouse eyes increases the IOP. We also show that acute Angptl7 silencing in adult mice lowers the IOP (~2-4 mmHg), reproducing the observations in knockout mice. Collectively, our data suggest that ANGPTL7 is important for IOP homeostasis and is amenable to therapeutic modulation to help maintain a healthy IOP that can prevent onset or slow the progression of glaucoma.

AB - Glaucoma is a leading cause of blindness. Current glaucoma medications work by lowering intraocular pressure (IOP), a risk factor for glaucoma, but most treatments do not directly target the pathological changes leading to increased IOP, which can manifest as medication resistance as disease progresses. To identify physiological modulators of IOP, we performed genome- and exome-wide association analysis in >129,000 individuals with IOP measurements and extended these findings to an analysis of glaucoma risk. We report the identification and functional characterization of rare coding variants (including loss-of-function variants) in ANGPTL7 associated with reduction in IOP and glaucoma protection. We validated the human genetics findings in mice by establishing that Angptl7 knockout mice have lower (~2 mmHg) basal IOP compared to wild-type, with a trend towards lower IOP also in heterozygotes. Conversely, increasing murine Angptl7 levels via injection into mouse eyes increases the IOP. We also show that acute Angptl7 silencing in adult mice lowers the IOP (~2-4 mmHg), reproducing the observations in knockout mice. Collectively, our data suggest that ANGPTL7 is important for IOP homeostasis and is amenable to therapeutic modulation to help maintain a healthy IOP that can prevent onset or slow the progression of glaucoma.

U2 - 10.1038/s42003-022-03932-6

DO - 10.1038/s42003-022-03932-6

M3 - Journal article

C2 - 36192519

AN - SCOPUS:85139177016

VL - 5

JO - Communications Biology

JF - Communications Biology

SN - 2399-3642

M1 - 1051

ER -

ID: 325636208

Institut for Klinisk Medicin