Tunable degrees of neurodegeneration in rats based on microsphere-induced models of chronic glaucoma

Abstract

This study compares four different animal models of chronic glaucoma against normal aging over 6 months. Chronic glaucoma was induced in 138 Long–Evans rats and compared against 43 aged-matched healthy rats. Twenty-five rats received episcleral vein sclerosis injections (EPIm cohort) while the rest were injected in the eye anterior chamber with a suspension of biodegradable microspheres: 25 rats received non-loaded microspheres (N-L Ms cohort), 45 rats received microspheres loaded with dexamethasone (MsDexa cohort), and 43 rats received microspheres co-loaded with dexamethasone and fibronectin (MsDexaFibro cohort). Intraocular pressure, neuroretinal function, structure and vitreous interface were evaluated. Each model caused different trends in intraocular pressure, produced specific retinal damage and vitreous signals. The steepest and strongest increase in intraocular pressure was seen in the EPIm cohort and microspheres models were more progressive. The EPIm cohort presented the highest vitreous intensity and percentage loss in the ganglion cell layer, the MsDexa cohort presented the greatest loss in the retinal nerve fiber layer, and the MsDexaFibro cohort presented the greatest loss in total retinal thickness. Function decreased differently among cohorts. Using biodegradable microspheres models it is possible to generate tuned neurodegeneration. These results support the multifactorial nature of glaucoma based on several noxa.