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Ramez I. Haddadin, Dong-Jin Oh, Douglas J. Rhee; SPARC Is Not Involved In Latanoprost-induced Changes In Intraocular Pressure, Nor In Trabecular Meshwork Or Ciliary Body Smooth Muscle Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5112.
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© ARVO (1962-2015); The Authors (2016-present)
SPARC, a matricellular protein, has been shown to induce extracellular matrix (ECM) production and suppress matrix metalloproteinase (MMP) activity. SPARC-null mice exhibit a 15-20% lower intraocular pressure (IOP). Prostaglandin analogues increase the biosynthesis of MMPs and shift the balance of MMPs and tissue inhibitors of MMPs towards greater activity leading to a reduction of ECM and subsequent increase of aqueous drainage through uveoscleral and conventional pathways. We hypothesized that SPARC is part of the mechanistic response to latanoprost (LAT) that results in the lower IOP.
Six to eight week-old wild type (WT) and SPARC-null mice were fed ad lib. Under dim red-light illumination, mice were treated with 4 microliters of 0.005% LAT in the treated eye and PBS in the contralateral eye, between 20:00 and 22:00. IOP measurements were performed 2 hrs after eye drop administration under anesthesia using the Tonolab. We also incubated human trabecular meshwork (TM) and ciliary body smooth muscle (CBSM) cells with LAT for 1, 3, and 7 days. Expression of SPARC mRNA, cell/ECM-bound protein, and soluble protein secreted into the culture media were measured by real-time RT-PCR, western blotting, and ELISA, respectively.
The average IOPs of untreated and treated WT eyes were 22.9+/-3.6 mm Hg and 19.4+/-3.5, respectively, a difference of 15.2% (p=10-7, n=20). The average IOPs of untreated and treated SPARC-null eyes were 18.2+/-1.7 mm Hg and 15.1+/-1.7, respectively, a difference of 16.5% (p=10-8, n=30). SPARC-null mice had a 20% lower IOP than WT (p=10-7). The percent decrease in IOPs of treated eyes was not different between WT and SPARC-null mice (p=0.64). Compared to control-treated TM and CBSM cells, cells incubated with LAT did not show significant changes in SPARC mRNA, cell/ECM-bound protein, or soluble, secreted protein levels at 1-, 3- and 7-days (p>0.05, n=5).
Administration of LAT reduced mouse IOPs; however, there was no difference in the degree of IOP lowering in SPARC-null mice. TM and CBSM cells incubated with LAT did not alter SPARC mRNA or protein content. Although SPARC may be implicated in pathways resulting in IOP elevation, it is unlikely to play a significant role in prostaglandin-induced IOP lowering.
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