Peripheral Latanoprost Administration Lowers Intraocular Pressure in the Wistar Rat

Abstract

Purpose: Instillation of latanoprost eye drops into the conjunctival sac to lower intraocular pressure (IOP) is the most frequently used treatment for primary open-angle glaucoma. The aim of this study was to evaluate the influence of latanoprost on IOP in the rat when applied peripherally. Methods: A rodent-dedicated tonometer was used to measure IOP in conscious adult male normotensive Wistar rats habituated to the measurement procedure. Commercially available 0.005% latanoprost solutions were continuously delivered to the periphery of the eye over 7 days using mini-pumps inserted subcutaneously in the animal's back, and IOP was measured daily. For comparison, a solution containing an equimolar concentration of latanoprost acid, an active compound of latanoprost, was similarly infused into the eyes of different Wistar rats. Results: Continuous subcutaneous infusion of latanoprost gradually decreased the IOP; the stable nadir of IOP, which was 20% lower than that prior to the start of infusion, was reached on day 3. The effect was statistically significant and fully reversed 2 days after cessation of drug delivery. Continuous subcutaneous application of the solution containing an equimolar amount of latanoprost acid did not appreciably influence the IOP. Conclusion: Subcutaneous continuous delivery of latanoprost decreased the IOP in the conscious normotensive Wistar rats in this study. If this effect is confirmed in humans, it may open the possibility of using peripheral systems of drug delivery, which could significantly improve patient compliance.

Changes of Ocular Dimensions as a Marker of Disease Progression in a Murine Model of Pigmentary Glaucoma

“…A rodent-dedicated rebound tonometer (TonoLab; Icare, Finland) was used for IOP measurements as we described previously ( Fiedorowicz et al., 2018 ; Świątkiewicz et al., 2020 ). In brief, the probe tip was situated in the long axis of the eye at 1 mm to 2 mm distance from the eye.…”

Development of the Latanoprost Solid Delivery System Based on Poly(l-lactide-co-glycolide-co-trimethylene carbonate) with Shape Memory for Glaucoma Treatment

“…For topical injections, the gel form is slightly similar to a solution, while nanoparticles often do not provide an opportunity to introduce the appropriate dose of the medicinal substance, and the large surface area often results in a burst effect. It should be pointed out that continuous subcutaneous infusion of 0.005% LTP solution over 7 days using mini pumps inserted in the backs of adult male normotensive Wistar rats effectively lowered intraocular pressure [32]. The solid biodegradable formulations seem to be the most appropriate.…”