Functional and morphologic study of retinal hypoperfusion injury induced by bilateral common carotid artery occlusion in rats

Abstract

Retinal hypoperfusion injury is the pathophysiologic basis of ocular ischemic syndrome (OIS) which often leads to severe visual loss. In this study, we aimed to establish a rat model of retinal chronic hypoperfusion by bilateral common carotid artery occlusion (BCCAO) and observe changes in the retinal function and morphology. We found that model rats showed retinal arteriosclerosis, slight dilated retinal vein, small hemangiomas, hemorrhages, vascular segmental filling, and nonperfused areas after 2 weeks of BCCAO. In the model rats, the retinal circulation time was significantly prolonged by fluorescein fundus angiography (FFA), the latency of a and b waves was delayed and the amplitude was decreased significantly at each time point by electroretinogram (ERG), and the perfusion of the eyes continued to reduced. Morphologic and ultrastructural changes covered that the retinal ganglion cells (RGCs) presented obvious apoptosis and the thickness in the retinal layers were significantly thinner. Collectively, these findings suggested that BCCAO induced retinal hypoperfusion injury in the model rats, thus providing an ideal animal model for the study of OIS.

Retinal dysfunction induced in a mouse model of unilateral common carotid artery occlusion

“…Full-size DOI: 10.7717/peerj.11665/fig- 5 et Qin et al, 2019;Sun et al, 2019;Yamamoto et al, 2006), milder retinal ischemic stress is observed in this UCCAO model. In this regard, retinal thinning was not dramatically observed in a short-term period even though there was retinal cell death.…”

“…It is associated with a huge range of clinical ocular disorders and diseases such as diabetic retinopathy, glaucoma, optic neuropathies and stroke ( Dattilo, Newman & Biousse, 2018 ; Fouda et al, 2020 ; Minhas, Morishita & Anand, 2012 ; Osborne et al, 2004 ). As oxygen (directly referred to as “blood”) in the retina is supplied through the ophthalmic artery originated from the internal carotid artery, one of two branches of the common carotid artery (CCA), animal models by common carotid artery occlusion or stenosis (CCAO or CCAS) have been used to understand the pathogenesis of retinal ischemia ( Crespo-Garcia et al, 2018 ; Davidson et al, 2000 ; Lavinsky et al, 2006 ; Lee et al, 2020b ; Qin et al, 2019 ; Sun et al., 2019 ; Venkat, Chopp & Chen, 2015 ; Wellons Iii et al., 2000 ; Yamamoto et al, 2006 ; Yang et al, 1997 ).…”

Fenofibrate Protects against Retinal Dysfunction in a Murine Model of Common Carotid Artery Occlusion-Induced Ocular Ischemia

“…Murine experimental models of carotid artery occlusion have been used to unravel pathological mechanisms for ocular ischemia [ 9 , 10 , 11 , 12 , 13 , 14 ]. Anatomically, the central retinal artery is derived from the ophthalmic artery, one of the branches of the internal carotid artery of the common carotid artery.…”

“…Therefore, carotid artery occlusion could potentially induce CRAO, finally leading to ocular ischemia and vision loss [ 15 , 16 ]. Bilateral common carotid artery occlusion to induce ocular ischemia has been applied to rats, in that the circle of Willis in rats is well-organized [ 9 , 10 , 11 , 12 , 13 , 17 ]. However, several studies reported that bilateral common carotid artery occlusion could not be applicable to mice with a high rate of death (almost 100%) because of a lack of posterior communicating arteries in the circle of Willis in mice [ 14 , 18 , 19 ].…”

Chronic stepwise cerebral hypoperfusion differentially induces synaptic proteome changes in the frontal cortex, occipital cortex, and hippocampus in rats

“…BCCAO also induces chronic ocular ischemia as the blood supply of the highly vascularized rodent retina comes from the internal carotid artery 20 . The retrograde neurodegeneration of the visual system results in the dysfunction of cortical neurons 21,22 . It could cause extensive structural remodeling in the visual cortex affecting the hypoperfusion-induced changes of the cortical proteome.…”