Elevated intraocular pressure causes inner retinal dysfunction before cell loss in a mouse model of experimental...

Area of Science:

• Ophthalmology
• Neuroscience
• Physiology

Background:

• Ocular hypertension (OHT) is a primary risk factor for glaucoma.
• Understanding the early functional and structural changes in OHT is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the relationship between intraocular pressure (IOP), retinal histology, and retinal function in a mouse model of chronic, mild ocular hypertension.
• To establish a reproducible model for studying early glaucomatous changes.

Main Methods:

• Ocular hypertension was induced in mice via anterior chamber injection of polystyrene beads.
• Intraocular pressure (IOP) was monitored using a rebound tonometer.
• Retinal ganglion cell (RGC) counts and histology were assessed using neurobiotin labeling and TO-PRO3 staining.
• Retinal function was evaluated using serial dark-adapted electroretinograms (ERGs), including a-wave, b-wave, and scotopic threshold responses (STRs).

Main Results:

• Polystyrene bead injection successfully induced and maintained elevated IOP for at least 3 months.
• Mild, progressive reduction in RGCs and increased axial length were observed.
• Early alterations in retinal electrical function, specifically a decrease in normalized positive scotopic threshold responses (pSTR), were detected before significant histologic changes.

Conclusions:

• The polystyrene bead model effectively recapitulates key aspects of human ocular hypertension and glaucoma.
• Early functional changes in retinal electrical activity precede detectable histologic damage in this model.
• Glaucoma associated with elevated IOP may involve early disruption of retinal synaptic function.