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Arginine Supplementation Promotes Extracellular Matrix and Metabolic Changes in Keratoconus

Keratoconus (KC) is a common corneal ectatic disease that affects 1:500–1:2000 people worldwide and is associated with a progressive thinning of the corneal stroma that may lead to severe astigmatism and visual deficits. Riboflavin-mediated collagen crosslinking currently remains the only approved t...

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Autores principales: McKay, Tina B., Priyadarsini, Shrestha, Rowsey, Tyler, Karamichos, Dimitrios
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394349/
https://www.ncbi.nlm.nih.gov/pubmed/34440845
http://dx.doi.org/10.3390/cells10082076
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author McKay, Tina B.
Priyadarsini, Shrestha
Rowsey, Tyler
Karamichos, Dimitrios
author_facet McKay, Tina B.
Priyadarsini, Shrestha
Rowsey, Tyler
Karamichos, Dimitrios
author_sort McKay, Tina B.
collection PubMed
description Keratoconus (KC) is a common corneal ectatic disease that affects 1:500–1:2000 people worldwide and is associated with a progressive thinning of the corneal stroma that may lead to severe astigmatism and visual deficits. Riboflavin-mediated collagen crosslinking currently remains the only approved treatment to halt progressive corneal thinning associated with KC by improving the biomechanical properties of the stroma. Treatments designed to increase collagen deposition by resident corneal stromal keratocytes remain elusive. In this study, we evaluated the effects of arginine supplementation on steady-state levels of arginine and arginine-related metabolites (e.g., ornithine, proline, hydroxyproline, spermidine, and putrescine) and collagen protein expression by primary human corneal fibroblasts isolated from KC and non-KC (healthy) corneas and cultured in an established 3D in vitro model. We identified lower cytoplasmic arginine and spermidine levels in KC-derived constructs compared to healthy controls, which corresponded with overall higher gene expression of arginase. Arginine supplementation led to a robust increase in cytoplasmic arginine, ornithine, and spermidine levels in controls only and a significant increase in collagen type I secretion in KC-derived constructs. Further studies evaluating safety and efficacy of arginine supplementation are required to elucidate the potential therapeutic applications of modulating collagen deposition in the context of KC.
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spelling pubmed-83943492021-08-28 Arginine Supplementation Promotes Extracellular Matrix and Metabolic Changes in Keratoconus McKay, Tina B. Priyadarsini, Shrestha Rowsey, Tyler Karamichos, Dimitrios Cells Article Keratoconus (KC) is a common corneal ectatic disease that affects 1:500–1:2000 people worldwide and is associated with a progressive thinning of the corneal stroma that may lead to severe astigmatism and visual deficits. Riboflavin-mediated collagen crosslinking currently remains the only approved treatment to halt progressive corneal thinning associated with KC by improving the biomechanical properties of the stroma. Treatments designed to increase collagen deposition by resident corneal stromal keratocytes remain elusive. In this study, we evaluated the effects of arginine supplementation on steady-state levels of arginine and arginine-related metabolites (e.g., ornithine, proline, hydroxyproline, spermidine, and putrescine) and collagen protein expression by primary human corneal fibroblasts isolated from KC and non-KC (healthy) corneas and cultured in an established 3D in vitro model. We identified lower cytoplasmic arginine and spermidine levels in KC-derived constructs compared to healthy controls, which corresponded with overall higher gene expression of arginase. Arginine supplementation led to a robust increase in cytoplasmic arginine, ornithine, and spermidine levels in controls only and a significant increase in collagen type I secretion in KC-derived constructs. Further studies evaluating safety and efficacy of arginine supplementation are required to elucidate the potential therapeutic applications of modulating collagen deposition in the context of KC. MDPI 2021-08-13 /pmc/articles/PMC8394349/ /pubmed/34440845 http://dx.doi.org/10.3390/cells10082076 Text en © 2021 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
McKay, Tina B.
Priyadarsini, Shrestha
Rowsey, Tyler
Karamichos, Dimitrios
Arginine Supplementation Promotes Extracellular Matrix and Metabolic Changes in Keratoconus
title Arginine Supplementation Promotes Extracellular Matrix and Metabolic Changes in Keratoconus
title_full Arginine Supplementation Promotes Extracellular Matrix and Metabolic Changes in Keratoconus
title_fullStr Arginine Supplementation Promotes Extracellular Matrix and Metabolic Changes in Keratoconus
title_full_unstemmed Arginine Supplementation Promotes Extracellular Matrix and Metabolic Changes in Keratoconus
title_short Arginine Supplementation Promotes Extracellular Matrix and Metabolic Changes in Keratoconus
title_sort arginine supplementation promotes extracellular matrix and metabolic changes in keratoconus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394349/
https://www.ncbi.nlm.nih.gov/pubmed/34440845
http://dx.doi.org/10.3390/cells10082076
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