scholarly journals Retinal Degeneration in a Murine Model of Retinal Ischemia by Unilateral Common Carotid Artery Occlusion

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Deokho Lee ◽  
Ayaka Nakai ◽  
Yukihiro Miwa ◽  
Yohei Tomita ◽  
Naho Serizawa ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Retinal Degeneration ◽  
Murine Model ◽  
Common Carotid Artery ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Ischemia ◽  
Artery Occlusion ◽  
Carotid Artery Occlusion ◽  
Common Carotid Artery Occlusion

Retinal degeneration is a progressive retinal damage in ocular vascular diseases. There are several reasons for this, such as occlusion of arteries or veins, diabetic retinopathy, or hereditary retinal diseases. To study pathological mechanisms of retinal degeneration, it is required to develop experimentally reproducible and clinically relevant models. In our previous studies, we developed a murine model of retinal hypoperfusion by unilateral common carotid artery occlusion (UCCAO) which mimics the pathophysiology of ocular ischemic syndrome (OIS) in humans, and described broad pathological mechanisms in the retina after UCCAO. However, there still remain missing pieces of the ocular pathologic process by UCCAO. In this study, we examined those unfound mechanisms. UCCAO was performed on adult mice. Ocular dysfunctions, histological deficits, and inflammation were examined after UCCAO, compared with sham-operated mice. Evaluation values were analyzed by electrophysiological, histological, and molecular biological methods. Eyelid drooping was permanently seen after UCCAO. Induction time point of acute reversible cataract under anesthesia was shortened. Retinal/visual dysfunctions were detected 2-4 weeks after UCCAO. Specifically, scotopic b-wave was more affected than a-wave, with the dysfunction of photopic b-wave. Impaired oscillatory potentials and visual evoked potential were constantly observed. Pathological Müller gliosis/inflammation was featured with NeuN-positive cell loss in the ganglion cell layer. Axial length, intraocular pressure, pupillary light reflex, and retinal pigment epithelium/choroidal thickness were not changed by UCCAO. A murine model of retinal ischemia by UCCAO can be useful for studying a series of degenerative process in the ischemic retina.

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

2021 ◽  
Vol 14 (3) ◽  
pp. 223
Author(s):  
Deokho Lee ◽  
Yohei Tomita ◽  
Yukihiro Miwa ◽  
Heonuk Jeong ◽  
Kiwako Mori ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Murine Model ◽  
Common Carotid Artery ◽  
Vision Loss ◽  
Artery Occlusion ◽  
Carotid Artery Occlusion ◽  
Fibroblast Growth Factor 21 ◽  
Retinal Dysfunction ◽  
Functional Changes ◽  
Common Carotid Artery Occlusion

Ocular ischemia is a common cause of blindness and plays a detrimental role in various diseases such as diabetic retinopathy, occlusion of central retinal arteries, and ocular ischemic syndrome. Abnormalities of neuronal activities in the eye occur under ocular ischemic conditions. Therefore, protecting their activities may prevent vision loss. Previously, peroxisome proliferator-activated receptor alpha (PPARα) agonists were suggested as promising drugs in ocular ischemia. However, the potential therapeutic roles of PPARα agonists in ocular ischemia are still unknown. Thus, we attempted to unravel systemic and ocular changes by treatment of fenofibrate, a well-known PPARα agonist, in a new murine model of ocular ischemia. Adult mice were orally administered fenofibrate (60 mg/kg) for 4 days once a day, followed by induction of ocular ischemia by unilateral common carotid artery occlusion (UCCAO). After UCCAO, fenofibrate was continuously supplied to mice once every 2 days during the experiment period. Electroretinography was performed to measure retinal functional changes. Furthermore, samples from the retina, liver, and blood were subjected to qPCR, Western blot, or ELISA analysis. We found that fenofibrate boosted liver function, increased serum levels of fibroblast growth factor 21 (FGF21), one of the neuroprotective molecules in the central nervous system, and protected against UCCAO-induced retinal dysfunction. Our current data suggest a promising fenofibrate therapy in ischemic retinopathies.

scholarly journals Pemafibrate Prevents Retinal Dysfunction in a Mouse Model of Unilateral Common Carotid Artery Occlusion

2021 ◽  
Vol 22 (17) ◽  
pp. 9408
Author(s):  
Deokho Lee ◽  
Yohei Tomita ◽  
Heonuk Jeong ◽  
Yukihiro Miwa ◽  
Kazuo Tsubota ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Carotid Artery ◽  
Common Carotid Artery ◽  
Oscillatory Potentials ◽  
Retinal Ischemia ◽  
Artery Occlusion ◽  
Carotid Artery Occlusion ◽  
Fibroblast Growth Factor 21 ◽  
Retinal Dysfunction ◽  
Common Carotid Artery Occlusion

Cardiovascular diseases lead to retinal ischemia, one of the leading causes of blindness. Retinal ischemia triggers pathological retinal glial responses and functional deficits. Therefore, maintaining retinal neuronal activities and modulating pathological gliosis may prevent loss of vision. Previously, pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, was nominated as a promising drug in retinal ischemia. However, a protective role of pemafibrate remains untouched in cardiovascular diseases-mediated retinal ischemia. Therefore, we aimed to unravel systemic and retinal alterations by treating pemafibrate in a new murine model of retinal ischemia caused by cardiovascular diseases. Adult C57BL/6 mice were orally administered pemafibrate (0.5 mg/kg) for 4 days, followed by unilateral common carotid artery occlusion (UCCAO). After UCCAO, pemafibrate was continuously supplied to mice until the end of experiments. Retinal function (a-and b-waves and the oscillatory potentials) was measured using electroretinography on day 5 and 12 after UCCAO. Moreover, the retina, liver, and serum were subjected to qPCR, immunohistochemistry, or ELISA analysis. We found that pemafibrate enhanced liver function, elevated serum levels of fibroblast growth factor 21 (FGF21), one of the neuroprotective molecules in the eye, and protected against UCCAO-induced retinal dysfunction, observed with modulation of retinal gliosis and preservation of oscillatory potentials. Our current data suggest a promising pemafibrate therapy for the suppression of retinal dysfunction in cardiovascular diseases.

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

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11665
Author(s):  
Deokho Lee ◽  
Heonuk Jeong ◽  
Yukihiro Miwa ◽  
Ari Shinojima ◽  
Yusaku Katada ◽  
...  
Keyword(s):  
Cell Death ◽  
Carotid Artery ◽  
Common Carotid Artery ◽  
Retinal Ischemia ◽  
Artery Occlusion ◽  
Carotid Artery Occlusion ◽  
Functional Changes ◽  
Functional Deficits ◽  
Retinal Thinning ◽  
Common Carotid Artery Occlusion

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.

scholarly journals Common Carotid Artery Occlusion Treatment: Revealing a Gap in the Current Guidelines

2013 ◽  
Vol 58 (3) ◽  
pp. 846 ◽  
Author(s):  
C. Klonaris ◽  
G.N. Kouvelos ◽  
M. Kafeza ◽  
A. Koutsoumpelis ◽  
A. Katsargyris ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Common Carotid Artery ◽  
Artery Occlusion ◽  
Carotid Artery Occlusion ◽  
Common Carotid Artery Occlusion ◽  
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