Neurodegeneration in chronic glaucoma analysed according to different hypertensive models induced in rats

Abstract

AbstractPurpose: To compare four different animal models of chronic glaucoma with normal ageing over 6 months.Methods: Chronic glaucoma was induced in 138 Long‐Evans rats and compared to 43 healthy rats (healthy cohort). Rats were injected in their right eye to increase intraocular pressure (IOP). 25 rats received biweekly episcleral vein sclerosis injections (EVS cohort) and the remaining rats received an intraocular injection with a suspension of biodegradables microspheres (Ms): 25 rats received no‐loaded Ms at 0‐2‐4‐8‐12‐16 and 20 weeks (Ms20/10 cohort), 45 rats received Ms loaded with dexamethasone at baseline and week 4 (MsDexa cohort), and 43 rats received Ms co‐loaded with dexamethasone and fibronectine at baseline (MsDexaFibro cohort), in the anterior chamber of the eye. IOP, functionality of neuroretina by electroretinography (ERG), structure of neuroretina and vitreous interface by optical coherence tomography (OCT) were analysed.Results: The EVS cohort showed the steepest and strongest increase in IOP, whereas the Ms models had a more progressive increase. Each model showed a specific retinal damage and vitreous signal in OCT. The EVS cohort experienced the highest vitreous intensity and percentage loss in ganglion cell layer, MsDexa in the retinal nerve fibre layer and MsDexaFibro in total thickness of the retina at 24 weeks of the study. Ganglion cells' signal using ERG was bigger in the glaucomatous cohorts compared to healthy rats.Conclusions: Different models of chronic glaucoma resulted in different curves of IOP and patterns of neuroretinal degeneration. Modulable degeneration was generated using models by the injection of biodegradable Ms. The biodegradable Ms models simulated accurately the neurodegeneration seen in human chronic glaucoma. Our results reinforced the multifactorial condition of glaucoma according to several noxa.