Animal Models Used to Simulate Retinal Artery Occlusion: A Comprehensive Review

Abstract

Purpose To present an overview of animal models of retinal artery occlusion (RAO). Methods Through a systematic literature search in PubMed and Embase, papers describing methods of inducing RAO in animal models were included. The identified methodologic approaches were presented in a narrative synthesis and compared with RAO in humans. Results In total, 83 papers reporting on 88 experiments were included. Six different species were used with rodents and monkeys being the most common, and a minority were performed using cats, dogs, rabbits, or pigs. The anatomy of pigs and monkeys resemble that of humans most closely. The two most frequently used methods were laser-induced occlusion or ligation of the arteries. Other methods included raised intraocular pressure, arterial clamping, administration of vasoconstricting agents, the use of an occluder, embolization, and endovascular approaches to induce occlusion. In general, occlusions lasted for only 30 to 90 minutes, often followed by reperfusion. Conclusions Although a broad range of methods have previously been used, they all have limitations. Preferably, the methods should imitate the human disease as closely as possible and avoid damaging other structures. Therefore, monkeys followed by pigs are to be preferred and ligation or clamping may be a suitable model in larger animals as there is a potential to isolate and occlude the retinal artery only. Being less invasive, laser-induced occlusion is another suitable approach. Translational Relevance This review aims at assisting researchers in deciding on the most ideal experimental setting, and thereby increase the translational value to human disease.

Epigallocatechin 3-Gallate Has a Neuroprotective Effect in Retinas of Rabbits with Ischemia/Reperfusion through the Activation of Nrf2/HO-1

“…It is important to consider that the model of the rabbit has some limitations to extrapolate our results to a clinical scenario. The rabbit eye presents morphological differences (lack of macula and a different retinal vasculature) [41] and the described molecular mechanisms for rI/R-induced damage for the human eye, have been not entirely characterized for this model. However, the objective was to demonstrate the neuroprotective effect of EGCG in rI/R determined by the grade of degeneration and cell death in retinal layers.…”

BPC 157 as a Therapy for Retinal Ischemia Induced by Retrobulbar Application of L-NAME in Rats

“…On the other hand, for the L-NAME retrobulbar application–induced retinal ischemia model and BPC 157 therapy in rats, we should emphasize the point that animal studies per se may be cautious regarding their results, although the role of an animal model is indispensable ( Minhas et al, 2015 ; Vestergaard et al, 2019 ). Also, we should emphasize the relative paucity of the BPC 157 clinical data ( Seiwerth et al, 2018 ; Sikiric et al, 2018 ; Sikiric et al, 2020 ; Gwyer et al, 2019 ).…”

Histological Assessment of Rat Retinas with Ischemia-Reperfusion Injury

“…CRAO could be achieved by different techniques, such as occlusion/ligation of arteries, temporary embolization using spheres, use of vasoconstrictors, etc. [10,13,16,17]. Several reasons make these procedures unfeasible for our purposes, including the risk of damaging surrounding tissues when dissecting and isolating retinal arteries, extreme difficulty in catheterizing these arteries, and inability to accurately control the ischemia period.…”

“…Various rat models that seek to reproduce retinal ischemic conditions are based on the administration of substances [10], photocoagulation [10,11], or more invasive and complex surgical procedures [10,12,13], which might mask the physiopathology of IRI. In this study, we propose a simple model for inducing retinal IRI, based on increasing intraocular hydrostatic pressure, which is easily reproducible and suitable for trials with systemic drugs seeking to reduce the damage caused by retinal reperfusion.…”