The outflow facility of SPARC KO and WT mice

Abstract

Purpose: Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that regulates intraocular pressure (IOP) through altering extracellular matrix (ECM) homeostasis within the trabecular meshwork (TM). We hypothesized that lower IOP previously observed in SPARC knockout (KO) mice is due to a higher outflow facility.

Methods: IOP was measured using a rebound tonometer between 4 and 7 minutes after the mice were anesthetized. Mouse outflow facility (C value) was determined by multiple flow rate infusion and episcleral venous pressure (Pe) measured by manometry. The animals were then euthanatized, eliminating aqueous formation rate (Fin) and uveoscleral outflow (Fu). C value was determined again (C_dead) while Fu and Fin were deduced. 35G needle was good for 6-week-old young mice.

Results: The IOP was 14.7±1.2 mmHg in SPARC KO mouse was lower than SPARC WT mouse 17.3±0.52 mmHg (p=0.0006, n=6, respectively). The C_alive of SPARC KO mice was 0.014±0.003 µL/min/mmHg, compared to the 0.010±0.001 µL/min/mmHg of the SPARC WT mice; the C_alive values for the SPARC KO mice were higher (p=0.0035). Pe values were 8.0±0.3 mmHg and 8.3±0.8 mmHg in SPARC KO mice and SPARC WT mice, respectively (p=0.35). Fu were 0.019±0.006 µL/min and 0.025±0.003 µL/min (p=0.23) for SPARC KO and WT mice, respectively. Fin were 0.114±0.002 µL/min and 0.117±0.017 µL/min (p=0.91) for SPARC KO and WT mice.

Conclusions: Our data identified that the lower IOP of SPARC KO mice is due to greater aqueous humor outflow. Collectively with prior studies demonstrating SPARC-induced ECM changes within the TM, these data add additional evidence to the importance of ECM turnover in the regulation of IOP.