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

PURPOSE:Secreted protein acidic and rich in cysteine 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 -/- 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 duanyu1842RC -/- 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 duanyu1842RC -/- mice were higher. Pe values were estimated to be 8.0 ± 0.2 mmHg and 8.3 ± 0.7 mmHg in duanyu1842RC -/- 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 duanyu1842RC -/- 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 duanyu1842RC -/- 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 duanyu1842RC -/- mice (p < 0.05). CONCLUSIONS:The lower IOP of duanyu1842RC -/- 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 duanyu1842RC -/- mice.

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