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Muhammad Abdulrazik; Evaluation of Recombinant Human Insulin-like Growth Factor-1 Effect on IOP in Ocular Normotensive Rabbits. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1511.
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Several macromolecules have been evaluated as ocular hypotensive agents with promising potency in some cases. However, optimizing dosing and route of administration parameters is still challenging while toxicity to retina and corneal endothelium remains a major concern. Attempts to study the merits of insulin like growth factor 1 (IGF-1) were discontinued in the past as supraphysiologic levels of IGF-1 produced diabetic-like retinal microangiopathy. The present study aims at investigating the effect of relatively moderate and safe doses of IGF-1 on IOP.
The present study comprises local ocular rhIGF-1 (Tercica Inc.) interventions in ocular normotensive, 2-2.5 kg, male albino rabbits. 3 routes of administration were investigated utilizing 3 pairs of 6 treated and 6 control animals. Treated and control animals received local dose to the right eye of 50 µl of rhIGF-1 (500 ng/µl) or balanced salt solution, respectively, 3 times per week. The intervention was done through intrascleral injection (1 mm away from upper limbus), corneal intrastromal injection (in upper cornea, 2 mm away from limbus), or through controlled topical administration on central cornea (via 5 mm cylinder placed on central cornea) for 1st, 2nd, and 3rd intervention groups respectively. End points were IOP (Tonopen AVIA, Reichert) and central corneal thickness (CCT) (SP 100, Tomey) at the end of the 9th week.
Intrastromal administration achieved best scores as IOP of the rhIGF-1 treated group (5.17±0.98 mmHg) was significantly lower than baseline (8.17±0.75; p .0039) and control group (7.83±0.75; p .0039). For intrascleral administration, IOP of the rhIGF-1 treated group (6.5±1.05) was also significantly lower than baseline (8.5±0.55; p .0082) and control group (8.83±1.17; p .0131). Topical corneal intervention scored least ocular hypotensive effect, as IOP of the rhIGF-1 treated group (7.17±1.17) was significantly lower than baseline (8.67±0.82; p .0453) but with non-statistically significant difference from control group (8.5±0.84; p .0656). Although 9th week CCT measurements in intrastromal group showed slight increase over baseline, differences were still non-statistically significant, as was the case with other 2 groups.
The superiority in IOP-lowering effect of intrastromal over topical rhIGF-1 reflects relatively poor penetration of rhIGF-1 through the intact cornea. Although intrascleral rhIGF-1 administration promises better availability at presumed target tissues the results suggest relatively limited diffusion from site of injection toward target tissues.
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