chronic glaucoma in rats induced by single injection of fibronectin‐loaded PLGA microspheres

Abstract

Purpose: To generate a model of chronic glaucoma in rats, by means of a single injection that simulates the pathology that occurs in humans. Methods: A total of 47 Long‐Evans rats of both sexes were used; 30 rats received an intracameral injection of a suspension of fibronectin‐loaded poly‐lactic‐glycolic acid microspheres into the right eye, and the other 17 served as controls. They were followed up for 24 weeks, evaluating intraocular pressure (IOP) with a rebound tonometer, neuro‐retinal structure by optical coherence tomography (OCT) with segmentation protocols for the analysis of the entire retina, the ganglion cell layer (GCL) and the peripapillary retinal nerve fibre layer (pRNFL); as well as retinal functionality by electroretinography (ERG). Results: The IOP of the induced eyes increased progressively and chronically (11.64 ± 1.43 to 21.89 ± 3.94 mmHg) compared to the controls (p = 0.025) and with higher levels than the contralateral eyes (p < 0.05) until week 20, when this trend reversed. The induced eyes showed fluctuations in OCT retinal thickness over time. A trend of less thickness in the retina and GCL was measured in the induced eye and its contralateral eye; but at the end of the study, greater thicknesses were quantified than in the control eyes (p = 0.036). In addition, a lower ERG signal was recorded in the induced eyes. Ganglion cell functionality progressively decreased and was lower than contralateral eyes and control eyes at 12 and 24 weeks (p < 0.05). Males showed higher IOP (p < 0.05), greater thicknesses in the retina and lesser in the GCL and pRNFL (p < 0.05), with decreased functionality at 12 and 24 weeks compared to females. Conclusions: A minimally invasive chronic glaucoma model was obtained using single‐injection by pharmaceutical technology, which produced a progressive increase in intraocular pressure and structural and functional neuro‐retinal damage.

Multi-loaded PLGA microspheres as neuroretinal therapy in a chronic glaucoma animal model

“…Figure 2. In vivo methodology on the animals was performed as in our previous works [35]. For details, please see Supplementary methods 2.…”

“…To avoid frequent interventions new glaucoma animal models based on the intraocular pressure elevation, and subsequently, retinal glaucomatous damage, by injection of loaded and non-loaded biodegradable microparticles in the anterior chamber of the eye have been proposed in the last years [31][32][33][34]. In the present work, one of the mentioned models has been selected for neuroprotection activity studies, where glaucomatous damage in the retina was observed over six months after a single intracameral injection of fibronectin (FN) loaded PLGA microspheres, mimicking the progression of the disease in humans [35]. The main advantage of this animal model is that the chronic retinal damage is created by a single injection of FN-loaded particles in the anterior chamber, with no damage of any other ocular structure, furthermore, this model allows to test intravitreal drug delivery systems for long periods.…”