Ocular hypertension model in Yucatan minipigs via multiple episcleral vein cauterizations

Abstract

Purpose : Pig eyes share many anatomical and physiological similarities with human eyes, including holangiotic retinal vasculature, cone photoreceptors presence in the outer retina, no tapetum lucidum, and a similar scleral thickness, rendering them a valuable model for glaucoma. The purpose of this study was to establish an ocular hypertension (OHT) model via multiple episcleral vein cauterizations to assess changes in intraocular pressure (IOP), retinal structure and function in Yucatan minipigs.

Methods : Seven Yucatan minipigs underwent two rounds of episcleral vein cauterization in both eyes. Three episcleral veins (dorsal, medial, and lateral) were cauterized first, followed by a second cauterization procedure of two episcleral veins (dorsal and lateral) after 7 weeks. IOP measurements were obtained pre-cauterization baseline and weekly after first cauterization using a Tonovet™ rebound tonometer. Fundus fluorescein angiography (FFA), optical coherence tomography (OCT) imaging, and electroretinography (ERG) were performed at various timepoints to assess the structural and functional changes in the retina.

Results : Episcleral vein cauterization produced moderate to pronounced increases in IOP in five of seven Yucatan minipigs after two rounds of cauterization. The first cauterization procedure induced transient IOP increase at week-5 and -6 followed by second cauterization at week 7 that induced significant increase in IOPs (One-way ANOVA, p≤0.05) remaining consistently high starting from week 10 (Baseline IOP = 22.10±2.17 mmHg vs 30.60±3.49 mmHg at week 5 vs 30.33±2.89 mmHg at week 13). The FFA showed tortuous retinal vessels and ischemic retinal areas after week 12. The OCT imaging showed that peripapillary retinal nerve fiber thickness and optic cup:disc ratios were not significantly changed over time. ERG analysis showed slightly reduced wave amplitudes at week 14 compared to the naïve animals (One-way ANOVA, p≤0.05).

Conclusions : Multiple episcleral vein cauterization can be used as a method for inducing OHT leading to retinal structure and function changes in Yucatan minipigs to screen and evaluate novel therapeutics for glaucoma.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.