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

Purpose 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 (C_live) was determined by multiple flow rate infusion, and episcleral venous pressure (P_e) was estimated by manometry. The animals were then euthanized, eliminating aqueous formation rate (F_in) and P_e. The C value was determined again (C_dead) while F_in was reduced to zero. Additional mice were euthanized for immunohistochemistry to analyze ECM components of the TM. Results The C_live and C_dead 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 C_live = 0.010 ± 0.002 μL/min/ mmHg and C_dead = 0.011 ± 0.002 μL/min/mmHg in the WT mice (p = 0.548, N/S), the C_live and C_dead values for the SPARC -/- mice were higher. P_e 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 (F_u) 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). F_in 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). 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.