Secreted protein acidic and rich in cysteine (SPARC) knockout mice have greater outflow facility
Autor: | Ling Yu, Yuxi Zheng, Brian James Liu, Min Hyung Kang, J. Cameron Millar, Douglas J Rhee |
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Rok vydání: | 2020 |
Předmět: |
Intraocular pressure
Physiology Biochemistry Laminin Medicine and Health Sciences Homeostasis Osteonectin Flow Rate Mice Knockout Extracellular Matrix Proteins Multidisciplinary biology Chemistry Physics Matricellular protein Classical Mechanics medicine.anatomical_structure Knockout mouse Physical Sciences Immunohistochemistry Medicine Biological Cultures Anatomy Rheology Research Article Science Fluid Mechanics Research and Analysis Methods Continuum Mechanics Aqueous Humor Ocular System medicine Animals Immunohistochemistry Techniques Intraocular Pressure Euthanasia Biology and Life Sciences Proteins Fluid Dynamics Cell Cultures Molecular biology Fibronectin Mice Inbred C57BL Histochemistry and Cytochemistry Techniques biology.protein Hydrodynamics Immunologic Techniques Eyes Trabecular meshwork Physiological Processes Collagens Head Cysteine |
Zdroj: | PLoS ONE PLoS ONE, Vol 15, Iss 11, p e0241294 (2020) |
ISSN: | 1932-6203 |
Popis: | PurposeSecreted 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.MethodsMouse 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.ResultsThe Clive and Cdead of SPARC -/- mice were 0.014 ± 0.002 μL/min/mmHg and 0.015 ± 0.002 μL/min/mmHg, respectively (p = 0.376, N/S). Compared to the Clive = 0.010 ± 0.002 μL/min/mmHg and Cdead = 0.011 ± 0.002 μL/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 μL/min and 0.022 ± 0.006 μL/min for SPARC -/- and WT mice, respectively (p = 0.561, N/S). Fin was 0.114 ± 0.002 μL/min and 0.120 ± 0.016 μL/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).ConclusionsThe 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. |
Databáze: | OpenAIRE |
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