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

Deokho Lee; Heonuk Jeong; Yukihiro Miwa; Ari Shinojima; Yusaku Katada; Kazuo Tsubota; Toshihide Kurihara

doi:10.7717/peerj.11665

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

PeerJ. 2021 Jun 21:9:e11665. doi: 10.7717/peerj.11665. eCollection 2021.

Authors

Deokho Lee^#^{1

2}, Heonuk Jeong^#^{1

2}, Yukihiro Miwa^{1

2

3}, Ari Shinojima^{1

2}, Yusaku Katada^{1

2}, Kazuo Tsubota^{2

4}, Toshihide Kurihara^{1

2}

Affiliations

¹ Laboratory of Photobiology, Keio University School of Medicine, Tokyo, Japan.
² Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
³ Animal eye-care, Tokyo Animal Eye Clinic, Tokyo, Japan.
⁴ Tsubota Laboratory, Inc., Tokyo, Japan.

^# Contributed equally.

Abstract

Background: Retinal ischemic stresses are associated with the pathogenesis of various retinal vascular diseases. To investigate pathological mechanisms of retinal ischemia, reproducible, robust and clinically significant experimental rodent models are highly needed. Previously, we established a stable murine model of chronic hypoperfusion retinal injuries by permanent unilateral common carotid artery occlusion (UCCAO) and demonstrated chronic pathological processes in the ischemic retina after the occlusion; however, retinal functional deficits and other acute retinal ischemic injuries by UCCAO still remain obscure. In this study, we attempted to examine retinal functional changes as well as acute retinal ischemic alterations such as retinal thinning, gliosis and cell death after UCCAO.

Methods: Adult mice (male C57BL/6, 6-8 weeks old) were subjected to UCCAO in the right side, and retinal function was primarily measured using electroretinography for 14 days after the surgery. Furthermore, retinal thinning, gliosis and cell death were investigated using optical coherence tomography, immunohistochemistry and TUNEL assay, respectively.

Results: Functional deficits in the unilateral right retina started to be seen 7 days after the occlusion. Specifically, the amplitude of b-wave dramatically decreased while that of a-wave was slightly affected. 14 days after the occlusion, the amplitudes of both waves and oscillatory potentials were significantly detected decreased in the unilateral right retina. Even though a change in retinal thickness was not dramatically observed among all the eyes, retinal gliosis and cell death in the unilateral right retina were substantially observed after UCCAO.

Conclusions: Along with previous retinal ischemic results in this model, UCCAO can stimulate retinal ischemia leading to functional, morphological and molecular changes in the retina. This model can be useful for the investigation of pathological mechanisms for human ischemic retinopathies and furthermore can be utilized to test new drugs for various ischemic ocular diseases.

Keywords: Carotid artery; Electroretinography; Hypoperfusion; Hypoxia; Ischemia; Ocular ischemic syndrome; Ophthalmic artery; Retina; Retinal gliosis; Stroke.

Grants and funding

This work was supported by Grants-in-Aid for Scientific Research (KAKENHI) (18K09424 to Toshihide Kurihara). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.