Abstract
Purpose :
The previously reported experimental pressure-dependent glaucoma animal models are mainly characterized by artificially occluding the aqueous outflow pathway by injecting certain materials or laser coagulating the trabecular meshwork. While these models have successfully induced mid- to long-term ocular hypertension and glaucomatous damage to the optic nerve and inner retina, the degree, onset, and duration of intraocular pressure (IOP) increase were somewhat unpredictable and variable among individual animals. The purpose of this study was to develop a minimally invasive large animal ocular hypertension-glaucoma model with controlled degree and duration of ocular hypertension without intraocular manipulation.
Methods :
A total of 6 purpose-bred dogs were included in the study. Under general anesthesia, a vascular loop was placed circumferentially approximately 2 mm posterior to the limbus of one eye. Pressure was applied externally to increase intraocular pressure (IOP) to the ranges of 31-40 mmHg (n=1), 36-45 mmHg (n=4), and 41-50 mmHg (n=1) for 3 hours at a time. The procedure was repeated 9 times. The contralateral eye served as the internal control. The changes were monitored through routine ophthalmic examinations, an obstacle course vision test, optical coherence tomography (OCT, Heidelberg), OCT angiography (OCTA), and electroretinography (ERG, Roland). At the end of the study, a histopathologic evaluation of the globes was conducted.
Results :
The 36-45 mmHg group exhibited inner retinal atrophy with decreased number of ganglion cells, decreased photopic and scotopic electroretinography (ERG), and diminished visual function under dim light conditions. In the 41-50 mmHg group, there was extensive full-thickness retinal atrophy, optic nerve rarefaction, extinguished ERG, and complete blindness. No marked changes in anatomy or function were detected in the 31-35 mmHg group.
Conclusions :
Intermittent IOP elevations to the targeted range induced various severity of retinal and optic nerve changes. IOP range of 36-45 mmHg appears to be adequate to induce inner retinal damage in dogs. This model may be useful to test various hypotheses, including neuroprotective treatment and biomechanical effect with controlled IOP elevation.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.