Relation of Retinal Oxygen Measures to Electrophysiology and Survival Indicators after Permanent, Incomplete Ischemia in Rats

Matei, Nathanael; Leahy, Sophie; Auvazian, Selin L; Thomas, Biju; Blair, Norman P.; Shahidi, Mahnaz

doi:10.1007/s12975-020-00799-9

Cited by 15 publications

(17 citation statements)

References 68 publications

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“…Second, the measured responses to ischemia may be dependent on the duration of anesthesia and age. The observed increase in DO 2 between 3 days and 7 days after BCCAO was not detected in related studies conducted under a longer duration of anesthesia in rats of different ages 17 . Third, the effect of BCCAO on choroidal circulation and recovery of retinal function which depends on changes in both retinal and choroidal hemodynamics were not evaluated in the current study.…”

Section: Discussioncontrasting

confidence: 67%

“…We have previously demonstrated that complete occlusion of the ophthalmic vessels followed by reperfusion results in reductions of total retinal blood flow (TRBF), oxygen delivery (DO 2 ), and oxygen metabolism (MO 2 ) 14 . Furthermore, we reported the effect of reductions in TRBF on DO 2 , MO 2 , and oxygen extraction fraction (OEF) immediately and after a few days of BCCAO [15][16][17] . However, there is lack of knowledge about alterations in DO 2 , MO 2 , and OEF due to long-term, incomplete reduction in TRBF (in our case long-term BCCAO), which is more relevant to clinical ischemic conditions than assessment of changes in these parameters immediately after complete loss of blood flow.…”

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confidence: 99%

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Retinal Oxygen Delivery, Metabolism, and Extraction Fraction during Long-Term Bilateral Common Carotid Artery Occlusion in Rats

Leahy

Farzad

Blair

et al. 2020

Sci Rep

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Retinal functional, biochemical, and anatomical changes have been previously reported in long-term experimental permanent bilateral common carotid artery occlusion (BccAo). the purpose of the current study was to investigate progressive reductions in retinal oxygen metabolism (Mo 2) due to inadequate compensation by oxygen delivery (Do 2) and extraction fraction (oef) after BccAo. twentynine rats were subjected to BCCAO and were imaged after 3 hours, 3 days, 7 days, or 14 days. Six rats underwent a sham procedure. Phosphorescence lifetime and blood flow imaging were performed in both eyes to measure retinal oxygen contents and total retinal blood flow, respectively. DO 2 , Mo 2 , and oef were calculated from these measurements. compared to the sham group, Do 2 and Mo 2 were reduced after all BCCAO durations. OEF was increased after 3 hours and 3 days of BCCAO, but was not different from the sham group after 7 and 14 days. Between 3 and 7 days of BCCAO, DO 2 increased, oef decreased, and there was no significant difference in MO 2. These findings may be useful to understand the pathophysiology of retinal ischemia.

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confidence: 67%

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confidence: 99%

Retinal Oxygen Delivery, Metabolism, and Extraction Fraction during Long-Term Bilateral Common Carotid Artery Occlusion in Rats

Leahy

Farzad

Blair

et al. 2020

Sci Rep

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“…In this regard, retinal thinning was not dramatically observed in a short-term period even though there was retinal cell death. In fact, retinal cell death in this UCCAO model is also seen weaker than that in other retinal injury models (Luo et al, 2020;Matei et al, 2020;Song et al, 2008). Long-term period studies may be necessary to observe histological injuries in the retina by UCCAO.…”

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confidence: 75%

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

Lee

Jeong

Miwa

et al. 2021

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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.

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“…Similar results were previously obtained using the same model of PA (Fernandez et al, 2020). It is understood that the a-wave represents the response of the photoreceptor cells, the OP that of the cells located in the inner nuclear layer, and the b-wave that of the ganglion cells (Jung et al, 2015;Matei et al, 2020;Zhai et al, 2020), thus indicating that PA imposes a negative influence at all levels of the visual axis. Interestingly, our study shows that application of hypothermia, either during or after PA, completely restored the a-wave and OP in all animals.…”

Section: Discussionmentioning

confidence: 99%

Hypothermic Shock Applied After Perinatal Asphyxia Prevents Retinal Damage in Rats

et al. 2021

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Perinatal asphyxia (PA) can cause retinopathy and different degrees of visual loss, including total blindness. In a rat model of PA, we have previously shown a protective effect of hypothermia on the retina when applied simultaneously with the hypoxic insult. In the present work, we evaluated the possible protective effect of hypothermia on the retina of PA rats when applied immediately after delivery. Four experimental groups were studied: Rats born naturally as controls (CTL), animals that were exposed to PA for 20 min at 37°C (PA), animals exposed to PA for 20 min at 15°C (HYP), and animals that were exposed to PA for 20 min at 37°C and, immediately after birth, kept for 15 min at 8°C (HYP-PA). To evaluate the integrity of the visual pathway, animals were subjected to electroretinography at 45 days of age. Molecular (real time PCR) and histological (immunohistochemistry, immunofluorescence, TUNEL assay) techniques were applied to the eyes of all experimental groups collected at 6, 12, 24, and 48 h, and 6 days after birth. PA resulted in a significant reduction in the amplitude of the a- and b-wave and oscillatory potentials (OP) of the electroretinogram. All animals treated with hypothermia had a significant correction of the a-wave and OP, but the b-wave was fully corrected in the HYP group but only partially in the HYP-PA group. The number of TUNEL-positive cells increased sharply in the ganglion cell layer of the PA animals and this increase was significantly prevented by both hypothermia treatments. Expression of the cold-shock proteins, cold-inducible RNA binding protein (CIRP) and RNA binding motif protein 3 (RBM3), was undetectable in retinas of the CTL and PA groups, but they were highly expressed in ganglion neurons and cells of the inner nuclear layer of the HYP and HYP-PA groups. In conclusion, our results suggest that a post-partum hypothermic shock could represent a useful and affordable method to prevent asphyxia-related vision disabling sequelae.

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Relation of Retinal Oxygen Measures to Electrophysiology and Survival Indicators after Permanent, Incomplete Ischemia in Rats

Cited by 15 publications

References 68 publications

Retinal Oxygen Delivery, Metabolism, and Extraction Fraction during Long-Term Bilateral Common Carotid Artery Occlusion in Rats

Retinal Oxygen Delivery, Metabolism, and Extraction Fraction during Long-Term Bilateral Common Carotid Artery Occlusion in Rats

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

Hypothermic Shock Applied After Perinatal Asphyxia Prevents Retinal Damage in Rats

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