Short-Time Ocular Ischemia Induces Vascular Endothelial Dysfunction and Ganglion Cell Loss in the Pig Retina

Zadeh, Jenia Kouchek; García-Bardon, Andreas; Hartmann, Erik K.; Pfeiffer, Norbert; Omran, Wael; Ludwig, Marion; Patzak, Andreas; Xia, Ning; Li, Huige; Gericke, Adrian

doi:10.3390/ijms20194685

Cited by 19 publications

(29 citation statements)

References 54 publications

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“…Subsequently, retinal arterioles were pressurized to 50 mmHg, visualized under brightfield conditions, and equilibrated for 30 min. Mesenteric small arteries/arterioles of the 6th and 7th order were isolated and measured as previously described for other small blood vessels with minor modifications [ 19 , 74 ]. Briefly, a mesenteric vascular tree was isolated and cleaned from surrounding tissue by fine-point tweezers and Vannas scissors.…”

Section: Methodsmentioning

confidence: 99%

Ablation of lysozyme M-positive cells prevents aircraft noise-induced vascular damage without improving cerebral side effects

et al. 2021

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Aircraft noise induces vascular and cerebral inflammation and oxidative stress causing hypertension and cardiovascular/cerebral dysfunction. With the present studies, we sought to determine the role of myeloid cells in the vascular vs. cerebral consequences of exposure to aircraft noise. Toxin-mediated ablation of lysozyme M+ (LysM+) myeloid cells was performed in LysMCreiDTR mice carrying a cre-inducible diphtheria toxin receptor. In the last 4d of toxin treatment, the animals were exposed to noise at maximum and mean sound pressure levels of 85 and 72 dB(A), respectively. Flow cytometry analysis revealed accumulation of CD45+, CD11b+, F4/80+, and Ly6G−Ly6C+ cells in the aortas of noise-exposed mice, which was prevented by LysM+ cell ablation in the periphery, whereas brain infiltrates were even exacerbated upon ablation. Aircraft noise-induced increases in blood pressure and endothelial dysfunction of the aorta and retinal/mesenteric arterioles were almost completely normalized by ablation. Correspondingly, reactive oxygen species in the aorta, heart, and retinal/mesenteric vessels were attenuated in ablated noise-exposed mice, while microglial activation and abundance in the brain was greatly increased. Expression of phagocytic NADPH oxidase (NOX-2) and vascular cell adhesion molecule-1 (VCAM-1) mRNA in the aorta was reduced, while NFκB signaling appeared to be activated in the brain upon ablation. In sum, we show dissociation of cerebral and peripheral inflammatory reactions in response to aircraft noise after LysM+ cell ablation, wherein peripheral myeloid inflammatory cells represent a dominant part of the pathomechanism for noise stress-induced cardiovascular effects and their central nervous counterparts, microglia, as key mediators in stress responses.

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Section: Methodsmentioning

confidence: 99%

Ablation of lysozyme M-positive cells prevents aircraft noise-induced vascular damage without improving cerebral side effects

et al. 2021

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“…ROS formation was determined in 10 μ m cryosections of the retina and optic nerve by dihydroethidium- (DHE-, 1 μ m) derived fluorescence according to a modified protocol for vascular cryosections ( n = 8 per genotype) [24]. In retinal sections, the fluorescence (518 nm/605 nm excitation/emission) was measured in blood vessels and in individual layers of the inner retina as previously described [25–27].…”

Section: Methodsmentioning

confidence: 99%

Apolipoprotein E Deficiency Causes Endothelial Dysfunction in the Mouse Retina

Zadeh

Zhutdieva

Laspas

et al. 2019

Oxidative Medicine and Cellular Longevity

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Objective Atherogenic lipoproteins may impair vascular reactivity consecutively causing tissue damage in multiple organs via abnormal perfusion and excessive reactive oxygen species generation. We tested the hypothesis that chronic hypercholesterolemia causes endothelial dysfunction and cell loss in the retina. Methods Twelve-month-old apolipoprotein E-deficient (ApoE-/-) mice and age-matched wild-type controls were used in this study (n = 8 per genotype for each experiment). Intraocular pressure, blood pressure, and ocular perfusion pressure were determined. Retinal arteriole responses were studied in vitro, and reactive oxygen and nitrogen species were quantified in the retinal and optic nerve cryosections. The expression of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and the NADPH oxidase isoforms, NOX1, NOX2, and NOX4, were determined in retinal cryosections by immunofluorescence microscopy. Pro- and antioxidant redox genes were quantified in retinal explants by PCR. Moreover, cell number in the retinal ganglion cell layer and axon number in the optic nerve was calculated. Results Responses to the endothelium-dependent vasodilator, acetylcholine, were markedly impaired in retinal arterioles of ApoE-/- mice (P < 0.01). LOX-1 (P = 0.0007) and NOX2 (P = 0.0027) expressions as well as levels of reactive oxygen species (P = 0.0022) were increased in blood vessels but not in other retinal structures. In contrast, reactive nitrogen species were barely detectable in both mouse genotypes. Messenger RNA for HIF-1α, VEGF-A, NOX1, and NOX2, but also for various antioxidant redox genes was elevated in the retina of ApoE-/- mice. Total cell number in the retinal ganglion cell layer did not differ between ApoE-/- and wild-type mice (P = 0.2171). Also, axon number in the optic nerve did not differ between ApoE-/- and wild-type mice (P = 0.6435). Conclusion Apolipoprotein E deficiency induces oxidative stress and endothelial dysfunction in retinal arterioles, which may trigger hypoxia in the retinal tissue. Oxidative stress in nonvascular retinal tissue appears to be prevented by the upregulation of antioxidant redox enzymes, resulting in neuron preservation.

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“…Retinal damage following retinal ischemic injury involves the activation of NOX2 [ 85 ]. In a model of ischemia/reperfusion (I/R) in pigs with an ischemic period of 12 min followed by 20 h of reperfusion, retinal arterioles developed endothelial dysfunction and displayed increased levels of HIF-1α, VEGF-A, NOX2 and ROS [ 140 ].…”

Section: Ros and Retinal/ocular Ischemiamentioning

confidence: 99%

Oxidative Stress and Vascular Dysfunction in the Retina: Therapeutic Strategies

et al. 2020

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Many retinal diseases, such as diabetic retinopathy, glaucoma, and age-related macular (AMD) degeneration, are associated with elevated reactive oxygen species (ROS) levels. ROS are important intracellular signaling molecules that regulate numerous physiological actions, including vascular reactivity and neuron function. However, excessive ROS formation has been linked to vascular endothelial dysfunction, neuron degeneration, and inflammation in the retina. ROS can directly modify cellular molecules and impair their function. Moreover, ROS can stimulate the production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) causing inflammation and cell death. However, there are various compounds with direct or indirect antioxidant activity that have been used to reduce ROS accumulation in animal models and humans. In this review, we report on the physiological and pathophysiological role of ROS in the retina with a special focus on the vascular system. Moreover, we present therapeutic approaches for individual retinal diseases targeting retinal signaling pathways involving ROS.

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Short-Time Ocular Ischemia Induces Vascular Endothelial Dysfunction and Ganglion Cell Loss in the Pig Retina

Cited by 19 publications

References 54 publications

Ablation of lysozyme M-positive cells prevents aircraft noise-induced vascular damage without improving cerebral side effects

Ablation of lysozyme M-positive cells prevents aircraft noise-induced vascular damage without improving cerebral side effects

Apolipoprotein E Deficiency Causes Endothelial Dysfunction in the Mouse Retina

Oxidative Stress and Vascular Dysfunction in the Retina: Therapeutic Strategies

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