Purchase this article with an account.
D.-J. Oh, R. I. Haddadin, D. J. Rhee; Replenishment of SPARC in SPARC-Null Mice Restores the Intraocular Pressures. Invest. Ophthalmol. Vis. Sci. 2010;51(13):980.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
We previously reported that SPARC-null mice have lower intraocular pressures (IOPs) than do their wild-type (WT) counterparts by reducing outflow resistance.1 Thus, SPARC may contribute to the regulation of IOP. We hypothesized that replacement of SPARC may restore the lower IOPs of the SPARC-null mice.
5 to 8-week old wild-type and SPARC-null mice were anesthetized by intraperitoneal injection of a ketamine/xylazine mixture. They were subsequently placed on a stereotaxic mouse adaptor, and the head was externally secured with two jaw holder cuffs as well as a tooth bar and nose clamp. A 35-gauge needle attached to 10-µL syringe was mounted onto microsyringe pump. The pump was mounted to a micromanipulator. 2 µL of hSPARC or control (ad-hSPARC or ad-control) adenovirus containing 107 infectious units/µL were injected transcorneally at a rate of 4 nL/s. After completing the injection, the needle was left in the anterior chamber for 5-10 minutes before removal. IOP was measured at 1 week intervals thereafter for 2 weeks. The animals were then sacrificed. The eyes were enucleated and fixed in preparation for cryo- and plastic sectioning. Transfer of hSPARC to trabecular meshwork was assessed by histology.
At the second week, the IOP in the ad-hSPARC injected SPARC-null mice increased 9.6 ± 9.2% (n = 4) above with their baseline. Three of the four animals responded with a 14.2 ± 0.2% increase in IOP while the IOP of the fourth animal decreased by 4.2%. The ad-control injected SPARC-null mice decreased IOP by 5.1 ± 10.2% (n = 4). The difference in IOP changes between the responding ad-hSPARC and ad-control eyes in SPARC-null eyes was statistically significant (p = 0.046).Interestingly, the ad-hSPARC injected WT mice did not experience a change in IOP form baseline, 0.5 ± 4.6% (n = 4). The ad-control injected WT mice decreased by 2.1 ± 11.4% (n = 4). The difference in IOP changes between the ad-hSPARC and ad-control eyes in the WT eyes was not significant (p = 0.69).
We showed that adenoviral delivery of hSPARC restored their IOPs in the SPARC-null mice comparable to the WT phenotype. SPARC may contribute to IOP regulation.Reference1. Haddadin RI, Oh DJ, Kang MH, Filippopoulos T, Gupta M, Hart L, Sage EH, Rhee DJ. SPARC-null mice exhibit lower intraocular pressures. Invest Ophthalmol Vis Sci. 2009;50:3771-3777.
This PDF is available to Subscribers Only