Biodegradable microspheres-induced models for chronic glaucoma: a comparison with the veins sclerosis model

Abstract

Purpose : Different animal models have been created to study glaucoma’s pathophysiology. However, most of them are based on a sudden increase of intraocular pressure (IOP) and it does not simulate the course of the disease. This study aims to compare two microspheres-induced animal models (MIm) with an episcleral vein sclerosis model (EPIm).

Methods : Both microspheres (Ms) were developed by extraction-evaporation method by single (Ms loaded with dexamethasone – MsDexa) or double (Ms loaded with dexamethasone and fibronectin – MsDexaFibro) emulsion. EPIm was performed in 25 Long-Evans rats with a total of 12 injections. To create the MIm, rats were injected into the anterior chamber of the eye. 45 rats received 2 injections of MsDexa and 43 rats received a single injection of MsDexaFibro. All animals were assessed in terms of IOP (rebound tonometer) and neuroretinal function (electroretinography -ERG-) and structure (optical coherence tomography -OCT-).

Results : MsDexa presented a particle size of 13.13 ± 0.60 μm and MsDexaFibro of 14.81 ± 0.30 μm, releasing the active substances for 10 weeks for dexamethasone and 24 weeks for fibronectin. Both MIm presented a progressive increase in IOP while EPIm showed a fast increase at earlier times. MsDexa cohort exhibited the greatest average IOP values throughout the 6-month study. All cohorts exhibited a progressive decrease in thickness recorded by OCT. Whole retina and ganglion cell layer thickness was lower in the EPIm cohort and RNFL in MsDexa at the end of the study. MsDexaFibro revealed greater fluctuations. Finally, ERG analysis showed decreased signals for MsDexa and MsDexaFibro cohorts in comparison with the EPIm cohort.

Conclusions : Loaded biodegradable Ms induced animals presented neuroretinal degeneration with a more progressive IOP increase and lower interventions (injections). These chronic animal models resulted a useful tool for the evaluation of neuroprotective drug delivery systems.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.