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Chronic Glaucoma Induced in Rats by a Single Injection of Fibronectin-Loaded PLGA Microspheres: IOP-Dependent and
Ines Munuera1, Alba Aragon-Navas2, Pilar Villacampa3
1Department of Ophthalmology, Miguel Servet University Hospital, Miguel Servet Ophthalmology Research Group (GIMSO), Aragon Health Research Institute (IIS Aragon), University of Zaragoza, 50009 Zaragoza, Spain.
International Journal of Molecular Sciences
|January 11, 2024
Summary
A novel animal model for chronic glaucoma was developed using biodegradable microspheres. This model allows for testing long-term therapies by inducing sustained intraocular pressure elevation and retinal damage.
Area of Science:
- Ophthalmology
- Neuroscience
- Biomaterials Science
Background:
- Chronic glaucoma is a leading cause of irreversible blindness.
- Existing animal models often do not fully recapitulate the slow, progressive nature of human glaucoma.
- Developing reliable models is crucial for testing novel, long-term therapeutic strategies.
Purpose of the Study:
- To establish and evaluate a new, minimally invasive animal model of chronic glaucoma.
- To utilize biodegradable fibronectin-loaded PLGA microspheres for inducing sustained ocular hypertension.
- To assess the model's utility for evaluating prolonged glaucoma therapies.
Main Methods:
- Induction of glaucoma in rats via a single injection of fibronectin-loaded PLGA microspheres (MsF) or non-loaded PLGA microspheres (Control).
- 24-week follow-up assessing intraocular pressure (IOP), optical coherence tomography (OCT), histology, and electroretinography.
- Comparative analysis between MsF, Control, and Healthy (non-injected) cohorts.
Main Results:
- Induced cohorts exhibited progressive IOP increase, reaching hypertensive values.
- All cohorts showed age-related ganglion cell layer (GCL) thickness decrease; however, injected cohorts had greater final GCL thickness.
- Histology revealed lower ganglion cell counts but higher astrogliosis and immune response in MsF group, correlating with functional damage detected by electroretinography.
- OCT was less sensitive in detecting early structural damage compared to histology and electroretinography.
Conclusions:
- A single injection of fibronectin-loaded biodegradable microspheres effectively induces a chronic glaucoma model in rats.
- This model demonstrates sustained IOP elevation and functional/structural retinal damage, suitable for long-term therapy testing.
- Early functional damage is detectable by electroretinography in the presence of astrogliosis, even when structural changes are not apparent via OCT.
