Secreted protein acidic and rich in cysteine (SPARC) knockout mice have greater outflow facility

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dc.creatorYu, Ling
dc.creatorZheng, Yuxi
dc.creatorLiu, Brian J.
dc.creatorKang, Min Hyung
dc.creatorMillar, J. Cameron
dc.creatorRhee, Douglas J.
dc.date.accessioned2022-10-14T14:32:31Z
dc.date.available2022-10-14T14:32:31Z
dc.date.issued2020-11-04
dc.description.abstractPURPOSE: Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that regulates intraocular pressure (IOP) by altering extracellular matrix (ECM) homeostasis within the trabecular meshwork (TM). We hypothesized that the lower IOP previously observed in SPARC -/- mice is due to a greater outflow facility. METHODS: Mouse outflow facility (Clive) was determined by multiple flow rate infusion, and episcleral venous pressure (Pe) was estimated by manometry. The animals were then euthanized, eliminating aqueous formation rate (Fin) and Pe. The C value was determined again (Cdead) while Fin was reduced to zero. Additional mice were euthanized for immunohistochemistry to analyze ECM components of the TM. RESULTS: The Clive and Cdead of SPARC -/- mice were 0.014 +/- 0.002 muL/min/mmHg and 0.015 +/- 0.002 muL/min/mmHg, respectively (p = 0.376, N/S). Compared to the Clive = 0.010 +/- 0.002 muL/min/mmHg and Cdead = 0.011 +/- 0.002 muL/min/mmHg in the WT mice (p = 0.548, N/S), the Clive and Cdead values for the SPARC -/- mice were higher. Pe values were estimated to be 8.0 +/- 0.2 mmHg and 8.3 +/- 0.7 mmHg in SPARC -/- and WT mice, respectively (p = 0.304, N/S). Uveoscleral outflow (Fu) was 0.019 +/- 0.007 muL/min and 0.022 +/- 0.006 muL/min for SPARC -/- and WT mice, respectively (p = 0.561, N/S). Fin was 0.114 +/- 0.002 muL/min and 0.120 +/- 0.016 muL/min for SPARC -/- and WT mice (p = 0.591, N/S). Immunohistochemistry demonstrated decreases of collagen types IV and VI, fibronectin, laminin, PAI-1, and tenascin-C within the TM of SPARC -/- mice (p < 0.05). CONCLUSIONS: The lower IOP of SPARC -/- mice is due to greater aqueous humor outflow facility through the conventional pathway. Corresponding changes in several matricellular proteins and ECM structural components were noted in the TM of SPARC -/- mice.
dc.description.sponsorshipDJR received grant EY 019654-01 from the National Eye Institute, https://www.nei.nih.gov and a grant from the Cleveland Eye Bank Foundation, https://cleyebankfoundation.org (unrestricted). This study was also supported by a P30 Core Grant P30-EY11373 from the National Eye Institute and a grant from Research to Prevent Blindness, https://www.rpbusa.org/rpb/
dc.identifier.citationYu, L., Zheng, Y., Liu, B. J., Kang, M. H., Millar, J. C., & Rhee, D. J. (2020). Secreted protein acidic and rich in cysteine (SPARC) knockout mice have greater outflow facility. PloS one, 15(11), e0241294. https://doi.org/10.1371/journal.pone.0241294
dc.identifier.issn1932-6203
dc.identifier.issue11
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31853
dc.identifier.volume15
dc.publisherPLOS
dc.relation.urihttps://doi.org/10.1371/journal.pone.0241294
dc.rights.holder© 2020 Yu et al.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePLoS One
dc.subject.meshAnimals
dc.subject.meshAqueous Humor / metabolism
dc.subject.meshExtracellular Matrix Proteins / metabolism
dc.subject.meshHydrodynamics
dc.subject.meshIntraocular Pressure
dc.subject.meshMice, Inbred C57BL
dc.subject.meshMice, Knockout
dc.subject.meshOsteonectin / deficiency
dc.subject.meshOsteonectin / metabolism
dc.subject.meshRheology
dc.titleSecreted protein acidic and rich in cysteine (SPARC) knockout mice have greater outflow facility
dc.typeArticle
dc.type.materialtext

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