Abstract
Purpose: :
Recently, it was reported that SPARC-null mice have lower IOPs than their wild-type counterparts. SPARC (secreted protein acidic and rich in cysteine) is a multifunctional glycoprotein that belongs to matricellular group of proteins. Reportedly, SPARC interacts with VEGFR-1 and have been shown to act by suppression of signaling through this receptor. Placenta Growth Factor-1 (PlGF-1) is a member of the VEGF family that is a pure agonist of VEGFR-1. The hypothesis for the study was that the interaction of PlGF-1 with VEGFR-1 may counteract some of SPARC effects on IOP. Therefore, the present study aims at investigating the effect of PlGF-1 on IOP.
Methods: :
36 normotensive male albino rabbits were divided into 3 groups, each with 6 treated and 6 control animals. Treated and control animals received once-daily local dose to the right eye of 20 µl of PlGF-1 (1 ng/µl) or balanced salt solution (BSS) respectively. The intervention was done through subconjunctival injection (2 mm away from upper limbus), intrastromal injection (in upper cornea, 2 mm away from limbus), or through controlled topical administration on central cornea (using 5 mm cylinder, placed on central cornea) for 1st, 2nd, and 3rd intervention groups respectively. Interventions were done daily at 10:00 AM and IOP (Tonopen AVIA, Reichert) and central corneal thickness (CCT) (SP 100, Tomey) were measured three times daily at 11:00 , 16:00 and 22:00.
Results: :
The following results represent 11:00 AM measurements in right eyes at 3 weeks after the initiation of PlGF-1/BSS intervention. For subconjunctival intervention, IOPs of the PlGF-1 treated group were higher than baseline (10.17±2.04 vs. 8.83±0.75 mmHg; p: .1495) and control group (10.17±2.04 vs. 8.67±0.52 mmHg; p: .1093). In contrast, for intrastromal intervention, IOPs of the PlGF-1 treated group were lower than baseline (6.17±0.98 vs. 9.17±0.75 mmHg; p: .0039) and control group (6.17±0.98 vs. 9.33±1.37 mmHg; p: .0039). Similarly, for topical corneal intervention, IOPs of the PlGF-1 treated group were also lower than baseline (6.67±1.21 vs. 9±1.26 mmHg; p: .0163) and control group (6.67±1.21 vs. 8.83±1.72 mmHg; p: .0306). In the intrastromal intervention, CCT measurements were 12.02 (p: .0039) and 5.07% (p: .0131) higher than baseline, for PlGF-1 and BSS respectively. In subconjunctival and topical corneal groups, differences in CCT from baseline were not statistically significant.
Conclusions: :
The effect of PlGF-1 intervention on IOP was dependent on its route of administration, implying opposite effects on different ocular tissues related to aqueous secretion and drainage.
Keywords: intraocular pressure • drug toxicity/drug effects • growth factors/growth factor receptors