Arginine Supplementation Promotes Extracellular Matrix and Metabolic Changes in Keratoconus

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dc.creatorMcKay, Tina B.
dc.creatorPriyadarsini, Shrestha
dc.creatorRowsey, Tyler
dc.creatorKaramichos, Dimitrios
dc.creator.orcid0000-0002-8761-3824 (Karamichos, Dimitrios)
dc.date.accessioned2022-09-20T20:19:46Z
dc.date.available2022-09-20T20:19:46Z
dc.date.issued2021-08-13
dc.description.abstractKeratoconus (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.
dc.description.sponsorshipThis research was funded by National Institute of Health (NEI) Grants 5R01EY028888 (DK) and T32EY023202.
dc.identifier.citationMcKay, T. B., Priyadarsini, S., Rowsey, T., & Karamichos, D. (2021). Arginine Supplementation Promotes Extracellular Matrix and Metabolic Changes in Keratoconus. Cells, 10(8), 2076. https://doi.org/10.3390/cells10082076
dc.identifier.issn2073-4409
dc.identifier.issue8
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31787
dc.identifier.volume10
dc.publisherMDPI
dc.relation.urihttps://doi.org/10.3390/cells10082076
dc.rights.holder© 2021 by the authors.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceCells
dc.subjectarginine
dc.subjectcollagen
dc.subjectcornea
dc.subjectextracellular matrix
dc.subjecthydroxyproline
dc.subjectkeratoconus
dc.subjectmetabolomics
dc.subjecttissue-engineered cornea
dc.subject.meshArginase / metabolism
dc.subject.meshArginine / metabolism
dc.subject.meshArginine / pharmacology
dc.subject.meshArginine / therapeutic use
dc.subject.meshCase-Control Studies
dc.subject.meshCell Culture Techniques
dc.subject.meshCells, Cultured
dc.subject.meshCollagen / metabolism
dc.subject.meshCollagen Type I / metabolism
dc.subject.meshCornea / cytology
dc.subject.meshCornea / metabolism
dc.subject.meshExtracellular Matrix / metabolism
dc.subject.meshFibroblasts / cytology
dc.subject.meshFibroblasts / drug effects
dc.subject.meshFibroblasts / metabolism
dc.subject.meshHumans
dc.subject.meshKeratoconus / drug therapy
dc.subject.meshKeratoconus / metabolism
dc.subject.meshKeratoconus / pathology
dc.subject.meshNitric Oxide Synthase / metabolism
dc.subject.meshOrnithine / metabolism
dc.subject.meshSpermidine / metabolism
dc.subject.meshUp-Regulation / drug effects
dc.titleArginine Supplementation Promotes Extracellular Matrix and Metabolic Changes in Keratoconus
dc.typeArticle
dc.type.materialtext

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