{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T17:33:41Z","timestamp":1793900021831,"version":"4.8.0"},"reference-count":76,"publisher":"Wiley","license":[{"start":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T00:00:00Z","timestamp":1573516800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014584","name":"University Medical Center Mainz","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014584","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2019,11,12]]},"abstract":"<jats:p><jats:italic>Objective<\/jats:italic>. 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. <jats:italic>Methods<\/jats:italic>. Twelve-month-old apolipoprotein E-deficient (ApoE-\/-) mice and age-matched wild-type controls were used in this study (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mi>n<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>8<\/mml:mn><\/mml:math> per genotype for each experiment). Intraocular pressure, blood pressure, and ocular perfusion pressure were determined. Retinal arteriole responses were studied <jats:italic>in vitro<\/jats:italic>, 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. <jats:italic>Results<\/jats:italic>. Responses to the endothelium-dependent vasodilator, acetylcholine, were markedly impaired in retinal arterioles of ApoE-\/- mice (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mi>P<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.01<\/mml:mn><\/mml:math>). LOX-1 (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mi>P<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.0007<\/mml:mn><\/mml:math>) and NOX2 (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><mml:mi>P<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.0027<\/mml:mn><\/mml:math>) expressions as well as levels of reactive oxygen species (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\"><mml:mi>P<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.0022<\/mml:mn><\/mml:math>) 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-1<jats:italic>\u03b1<\/jats:italic>, 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 (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M6\"><mml:mi>P<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.2171<\/mml:mn><\/mml:math>). Also, axon number in the optic nerve did not differ between ApoE-\/- and wild-type mice (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M7\"><mml:mi>P<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.6435<\/mml:mn><\/mml:math>). <jats:italic>Conclusion.<\/jats:italic> 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.<\/jats:p>","DOI":"10.1155\/2019\/5181429","type":"journal-article","created":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T23:31:23Z","timestamp":1573601483000},"page":"1-17","source":"Crossref","is-referenced-by-count":22,"title":["Apolipoprotein E Deficiency Causes Endothelial Dysfunction in the Mouse Retina"],"prefix":"10.1155","volume":"2019","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7463-3607","authenticated-orcid":true,"given":"Jenia Kouchek","family":"Zadeh","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayagozel B.","family":"Zhutdieva","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, 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