Evaluation of intravitreal injection of blank microspheres in a new chronic glaucoma rat model

Abstract

Purpose: To evaluate the intravitreal injection of PLGA/VitE non‐loaded microspheres as a potential platform to deliver neuroprotective active compounds in a chronic glaucoma animal model. In this model, a gradual increase in intraocular pressure (IOP) is observed due to physical and pharmacological damage to the trabecular meshwork by the intracameral injection of fibronectin‐loaded PLGA microspheres. Methods: Microspheres (Ms) employed to create the animal model were made by a double water‐in‐oil‐in‐water emulsion technique where fibronectin was included in the inner aqueous phase (F‐Ms). PLGA/VitE blank Ms (B‐Ms) were made by a single oil‐in‐water emulsion. Ms were characterized regarding mean particle size, particle size distribution and morphology. In vivo studies were carried out in Long‐Evans rats divided into two groups: control (n = 30) and treated (n = 20). To create the model, both groups received a single intracameral injection of F‐Ms suspension (10% w/v) in the right eye (RE). Two weeks later, a suspension of B‐Ms (5% w/v) was intravitreally injected into the RE (treated group). Clinical signs and IOP were assessed in both groups for 12 weeks. Results: Ms were spherical with a smooth surface and some porous in the case of F‐Ms and with a typical “golf‐ball like” surface in the case of B‐Ms. Size distribution was unimodal with an average size of 16.45 ± 0.37 μm for F‐Ms and 29.95 ± 0.42 μm for B‐Ms. Both ocular injections were well tolerated. In all cases, IOP values significantly increased over time (p < 0.05) with a rise of 6–7 mmHg at 12 weeks. No significant differences were found between the IOP in the treated and the control group. Conclusions: Intravitreal injections of B‐Ms were well tolerated and did not affect the IOP increase of the animal model. These findings underline the suitability of the glaucoma animal model created by the intracameral injection F‐Ms for the evaluation of treatments based on intravitreal injection of PLGA/VitE‐based microsystems.