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Transgene expression of Stanniocalcin-1 provides sustained intraocular pressure reduction by increasing outflow facility

Glaucoma is the leading cause of irreversible blindness worldwide. Therapies for glaucoma are directed toward reducing intraocular pressure (IOP), the leading risk factor and only reliable therapeutic target via topical medications or with procedural intervention including laser or surgery. Though t...

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Autores principales: Roddy, Gavin W., Roy Chowdhury, Uttio, Anderson, Kjersten J., Rinkoski, Tommy A., Hann, Cheryl R., Chiodo, Vince A., Smith, W. Clay, Fautsch, Michael P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154118/
https://www.ncbi.nlm.nih.gov/pubmed/35639753
http://dx.doi.org/10.1371/journal.pone.0269261
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author Roddy, Gavin W.
Roy Chowdhury, Uttio
Anderson, Kjersten J.
Rinkoski, Tommy A.
Hann, Cheryl R.
Chiodo, Vince A.
Smith, W. Clay
Fautsch, Michael P.
author_facet Roddy, Gavin W.
Roy Chowdhury, Uttio
Anderson, Kjersten J.
Rinkoski, Tommy A.
Hann, Cheryl R.
Chiodo, Vince A.
Smith, W. Clay
Fautsch, Michael P.
author_sort Roddy, Gavin W.
collection PubMed
description Glaucoma is the leading cause of irreversible blindness worldwide. Therapies for glaucoma are directed toward reducing intraocular pressure (IOP), the leading risk factor and only reliable therapeutic target via topical medications or with procedural intervention including laser or surgery. Though topical therapeutics are typically first line, less than 50% of patients take drops as prescribed. Sustained release technologies that decrease IOP for extended periods of time are being examined for clinical use. We recently identified Stanniocalcin-1, a naturally occurring hormone, as an IOP-lowering agent. Here, we show that a single injection into the anterior chamber of mice with an adeno-associated viral vector containing the transgene of stanniocalcin-1 results in diffuse and sustained expression of the protein and produces IOP reduction for up to 6 months. As the treatment effect begins to wane, IOP-lowering can be rescued with a repeat injection. Aqueous humor dynamic studies revealed an increase in outflow facility as the mechanism of action. This first-in-class therapeutic approach has the potential to improve care and reduce the rates of vision loss in the 80 million people worldwide currently affected by glaucoma.
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spelling pubmed-91541182022-06-01 Transgene expression of Stanniocalcin-1 provides sustained intraocular pressure reduction by increasing outflow facility Roddy, Gavin W. Roy Chowdhury, Uttio Anderson, Kjersten J. Rinkoski, Tommy A. Hann, Cheryl R. Chiodo, Vince A. Smith, W. Clay Fautsch, Michael P. PLoS One Research Article Glaucoma is the leading cause of irreversible blindness worldwide. Therapies for glaucoma are directed toward reducing intraocular pressure (IOP), the leading risk factor and only reliable therapeutic target via topical medications or with procedural intervention including laser or surgery. Though topical therapeutics are typically first line, less than 50% of patients take drops as prescribed. Sustained release technologies that decrease IOP for extended periods of time are being examined for clinical use. We recently identified Stanniocalcin-1, a naturally occurring hormone, as an IOP-lowering agent. Here, we show that a single injection into the anterior chamber of mice with an adeno-associated viral vector containing the transgene of stanniocalcin-1 results in diffuse and sustained expression of the protein and produces IOP reduction for up to 6 months. As the treatment effect begins to wane, IOP-lowering can be rescued with a repeat injection. Aqueous humor dynamic studies revealed an increase in outflow facility as the mechanism of action. This first-in-class therapeutic approach has the potential to improve care and reduce the rates of vision loss in the 80 million people worldwide currently affected by glaucoma. Public Library of Science 2022-05-31 /pmc/articles/PMC9154118/ /pubmed/35639753 http://dx.doi.org/10.1371/journal.pone.0269261 Text en © 2022 Roddy et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Roddy, Gavin W.
Roy Chowdhury, Uttio
Anderson, Kjersten J.
Rinkoski, Tommy A.
Hann, Cheryl R.
Chiodo, Vince A.
Smith, W. Clay
Fautsch, Michael P.
Transgene expression of Stanniocalcin-1 provides sustained intraocular pressure reduction by increasing outflow facility
title Transgene expression of Stanniocalcin-1 provides sustained intraocular pressure reduction by increasing outflow facility
title_full Transgene expression of Stanniocalcin-1 provides sustained intraocular pressure reduction by increasing outflow facility
title_fullStr Transgene expression of Stanniocalcin-1 provides sustained intraocular pressure reduction by increasing outflow facility
title_full_unstemmed Transgene expression of Stanniocalcin-1 provides sustained intraocular pressure reduction by increasing outflow facility
title_short Transgene expression of Stanniocalcin-1 provides sustained intraocular pressure reduction by increasing outflow facility
title_sort transgene expression of stanniocalcin-1 provides sustained intraocular pressure reduction by increasing outflow facility
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154118/
https://www.ncbi.nlm.nih.gov/pubmed/35639753
http://dx.doi.org/10.1371/journal.pone.0269261
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