Chronic Glaucoma Using Biodegradable Microspheres to Induce Intraocular Pressure Elevation. Six-Month Follow-Up

Area of Science:

• Ophthalmology
• Neuroscience
• Biomedical Engineering

Background:

• Glaucoma research requires robust animal models to study chronic ocular hypertension (OHT) and neuroretinal degeneration.
• Existing models may not fully replicate the progressive nature and human-like pathology of chronic glaucoma.
• A novel pre-trabecular model using biodegradable poly lactic-co-glycolic acid (PLGA) microspheres (Ms20/10) was developed to induce progressive OHT.

Purpose of the Study:

• To compare the efficacy and characteristics of two prolonged animal models of chronic glaucoma over 24 weeks.
• To evaluate a novel intracameral microsphere model (Ms20/10) against a traditional episcleral vein injection model (EPIm) for inducing OHT.
• To assess neuroretinal functionality and structural integrity in response to induced OHT in both models.

Main Methods:

• Two rat models were established: Ms20/10 (intracameral PLGA microspheres) and EPIm (episcleral vein injection), both inducing OHT.
• Ophthalmological assessments included clinical signs, intraocular pressure (IOP) measurements, and electroretinography (ERG) for neuroretinal function.
• Structural analysis utilized optical coherence tomography (OCT) for retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness, alongside histological examinations.

Main Results:

• Both Ms20/10 and EPIm models demonstrated progressive neuroretinal degeneration and contralateral eye effects (p < 0.05).
• The Ms20/10 model exhibited a more rapid IOP increase and superior ocular surface preservation compared to EPIm.
• While GCL thickness showed the largest percentage loss and RNFL the earliest/greatest loss in both models, EPIm tended towards more severe retinal pathology and functional deficits.

Conclusions:

• The intracameral biodegradable microsphere model (Ms20/10) more closely mimics human chronic glaucoma conditions.
• This model's less aggressive induction mechanism facilitates the study of glaucoma pathology over extended durations.
• Both models induce significant neuroretinal changes, but the microsphere model offers a more controlled and human-relevant platform for glaucoma research.