{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:09:36Z","timestamp":1789171776791,"version":"build-2803163510"},"reference-count":128,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T00:00:00Z","timestamp":1595980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["#16SDG3070001"],"award-info":[{"award-number":["#16SDG3070001"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01 EY029751-01\u2013NEI00072"],"award-info":[{"award-number":["R01 EY029751-01\u2013NEI00072"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Elevated plasma homocysteine (Hcy) level, known as hyperhomocysteinemia (HHcy) has been linked to different systemic and neurological diseases, well-known as a risk factor for systemic atherosclerosis and cardiovascular disease (CVD) and has been identified as a risk factor for several ocular disorders, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Different mechanisms have been proposed to explain HHcy-induced visual dysfunction, including oxidative stress, upregulation of inflammatory mediators, retinal ganglion cell apoptosis, and extracellular matrix remodeling. Our previous studies using in vivo and in vitro models of HHcy have demonstrated that Hcy impairs the function of both inner and outer blood retinal barrier (BRB). Dysfunction of BRB is a hallmark of vision loss in DR and AMD. Our findings highlighted oxidative stress, ER stress, inflammation, and epigenetic modifications as possible mechanisms of HHcy-induced BRB dysfunction. In addition, we recently reported HHcy-induced brain inflammation as a mechanism of blood\u2013brain barrier (BBB) dysfunction and pathogenesis of Alzheimer\u2019s disease (AD). Moreover, we are currently investigating the activation of glutamate receptor N-methyl-d-aspartate receptor (NMDAR) as the molecular mechanism for HHcy-induced BRB dysfunction. This review focuses on the studied effects of HHcy on BRB and the controversial role of HHcy in the pathogenesis of aging neurological diseases such as DR, AMD, and AD. We also highlight the possible mechanisms for such deleterious effects of HHcy.<\/jats:p>","DOI":"10.3390\/biom10081119","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T03:36:38Z","timestamp":1596080198000},"page":"1119","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Implication of Hyperhomocysteinemia in Blood Retinal Barrier (BRB) Dysfunction"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0245-8256","authenticated-orcid":false,"given":"Amany","family":"Tawfik","sequence":"first","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA"},{"name":"James and Jean Culver Vision Discovery Institute, MCG, Augusta University, Augusta, GA 30912, USA"},{"name":"Department of Cellular Biology and Anatomy, Medical College of Georgia (MCG), Augusta University, Augusta, GA 30912, USA"},{"name":"Department of Ophthalmology, MCG, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yara A.","family":"Samra","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA"},{"name":"James and Jean Culver Vision Discovery Institute, MCG, Augusta University, Augusta, GA 30912, USA"},{"name":"Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5167-3377","authenticated-orcid":false,"given":"Nehal M.","family":"Elsherbiny","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA"},{"name":"James and Jean Culver Vision Discovery Institute, MCG, Augusta University, Augusta, GA 30912, USA"},{"name":"Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Al-Shabrawey","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA"},{"name":"James and Jean Culver Vision Discovery Institute, MCG, Augusta University, Augusta, GA 30912, USA"},{"name":"Department of Cellular Biology and Anatomy, Medical College of Georgia (MCG), Augusta University, Augusta, GA 30912, USA"},{"name":"Department of Ophthalmology, MCG, Augusta University, Augusta, GA 30912, USA"},{"name":"Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1093\/clinchem\/44.2.311","article-title":"Enzyme conversion immunoassay for determining total homocysteine in plasma or serum","volume":"44","author":"Frantzen","year":"1998","journal-title":"Clin. 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