Purpose:
SPARC (secreted protein, acidic and rich in cysteine) is a matricellular protein that is highly expressed in remodeling tissues. We hypothesize that SPARC contributes to intraocular pressure (IOP) regulation by mediating extracellular matrix (ECM) turnover in the trabecular meshwork (TM) and ciliary body (CB). We compared the IOPs of SPARC-null (KO) mice and their corresponding wild-type (WT).
Methods:
C57Bl/6 x 129SvJ-crossed WT and KO mice were fed ad lib and housed under identical 12/12-hour light-dark cycles (on 7:00, off 19:00). Five to seven week-old WT and KO mice were anesthetized by intraperitoneal (IP) injection of a ketamine/xylazine mixture. A commercial rebound tonometer (TonoLab) was used to take 3 IOP measurements in each eye between 4 and 7 minutes after IP injection, as prior studies have shown this to be a period with stable IOP. Daytime measurements were taken between 11:00 and 15:00. Nighttime measurements were taken between 17:00 and 24:00 under red-light illumination. Animals were enucleated and stained for light microscopy (LM). Data are reported as mean ± standard deviation.
Results:
Mean daytime IOPs of WT and KO mice were 22.4 ± 2.5 mm Hg (n=18) and 17.5 ± 2.8 mm Hg (n=46), respectively. These daytime IOPs were statistically significantly different (p=10-8). Mean nighttime IOPs of WT and KO mice were 25.9 ± 3.6 mm Hg (n=6) and 17.8 ± 1.5 mm Hg (n=7), respectively. These nighttime IOPs were different (p=0.004). The day and night IOPs were different for WTs but not KOs (p= 0.047 and 0.79, respectively). Cannulation experiments validated the Tonolab measurements. Under LM, the canal of Schlemm, its endothelium, and the trabecular meshwork appeared similar between WT and KO mice.
Conclusions:
SPARC-null mice have significantly lower IOPs than their wild-type counterparts. SPARC plays an important role in the remodeling of adult tissues.
Keywords: intraocular pressure • extracellular matrix • trabecular meshwork