A Novel Animal Model of Hypoxic-Ischemic Retinal Injury

Abstract

Purpose : The purpose of our study is to better understand the correlation between hypoxia and ischemia by creating and characterizing an animal model of graded retinal hypoxic-ischemic injury using real-time intraocular pO₂ measurements and non-invasive imaging methods.

Methods : New Zealand pigmented rabbits (2-3kg) were divided into 4 groups of increasing ischemia severity based on intraocular pO₂ recordings. All procedures were in accordance with a protocol approved by the local IACUC and ARVO guidelines for animal care and use. The right eye of each animal is the experimental eye and the left eye acts as the control. Baseline imaging included fundus photos, fluorescein angiography, and optical coherence tomography. Graded ischemia was induced by elevating intraocular pressure (IOP) using a 27G needle inserted into the anterior chamber and attached to an infusion line. Infusion pressure was controlled with a Stellaris Vitrectomy System. An intraocular oxygen probe was then placed adjacent to a retinal vessel within 3-mm of the optic disk edge to measure real-time pO₂ readings during elevation of IOP over a 90-minute period. Follow-up studies were performed 3-7 days after the procedure.

Results : Figure 1 shows the average IOP and pO₂ measurements (±SE) as a function of time before and during ischemia. Animals in the 50-60% group (Group 1) and 80-90% group (Group 2) had an average of 57±4% reduction in pO₂ (N=8 eyes) and 89±3% reduction in pO₂ (N=11 eyes) from baseline respectively. The correlation of determination between IOP and average pO₂ was R²=0.9. For the 15 minutes prior to the onset of target ischemia, average sustained IOP for Group 1 and 2 was 37±11 mmHg and 44±8 mmHg (p<0.001) respectively. Rabbit IOP was elevated to an average of 43±6mmHg (Group 1) and 41±6mmHg (Group 2) during the 90-minute ischemic periods. Duration of time needed to achieve target pO₂ range was 13±6 minutes and 19±7 minutes (p=0.06) for Group 1 and 2 respectively.

Conclusions : Our results show that it is feasible to reliably and reproducibly create a graded hypoxic-ischemic insult to the rabbit retina. The duration of the insult is positively correlated with the severity of the hypoxia. This model will be useful for assessing the result of subclinical hypoxic-ischemic injury.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Figure 1.