{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:10:21Z","timestamp":1785215421518,"version":"3.55.0"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Ongoing Research Funding Support KSU","award":["ORF-2025-710"],"award-info":[{"award-number":["ORF-2025-710"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1007\/s12035-025-05411-5","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T11:16:34Z","timestamp":1764414994000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Altered Expression of Large Amino Acid Transporter (LAT1) and Branched-Chain Metabolic Enzymes in the Type 1 Diabetic Rat Retina"],"prefix":"10.1007","volume":"63","author":[{"given":"Dalia I.","family":"Aldosari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser A.","family":"Alshawakir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwar","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah S.","family":"Alhomida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad S.","family":"Ola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,29]]},"reference":[{"key":"5411_CR1","unstructured":"Federation ID (2024) Diabetic retinopathy: a call for global action. Available from:  https:\/\/idf.org\/news\/idf-iapb-dr-webinar\/. Accessed\u00a029 Jul 2024"},{"issue":"suppl_1","key":"5411_CR2","doi-asserted-by":"publisher","first-page":"s84","DOI":"10.2337\/diacare.27.2007.S84","volume":"27","author":"DS Fong","year":"2004","unstructured":"Fong DS et al (2004) Retinopathy in diabetes. Diabetes Care 27(suppl_1):s84\u2013s87","journal-title":"Diabetes Care"},{"issue":"6","key":"5411_CR3","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1007\/s11427-015-4856-x","volume":"58","author":"AJ Barber","year":"2015","unstructured":"Barber AJ (2015) Diabetic retinopathy: recent advances towards understanding neurodegeneration and vision loss. Sci China Life Sci 58(6):541\u2013549","journal-title":"Sci China Life Sci"},{"key":"5411_CR4","doi-asserted-by":"publisher","unstructured":"Al-Dosari DI et al (2017) Flavonoid naringenin attenuates oxidative stress, apoptosis and improves neurotrophic effects in the diabetic rat retina. Nutrients. https:\/\/doi.org\/10.3390\/nu9101161","DOI":"10.3390\/nu9101161"},{"issue":"1","key":"5411_CR5","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/s12640-019-00018-w","volume":"36","author":"MS Ola","year":"2019","unstructured":"Ola MS, Alhomida AS, LaNoue KF (2019) Gabapentin attenuates oxidative stress and apoptosis in the diabetic rat retina. Neurotox Res 36(1):81\u201390","journal-title":"Neurotox Res"},{"issue":"3","key":"5411_CR6","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1007\/BF00429777","volume":"14","author":"R Frayser","year":"1978","unstructured":"Frayser R, Buse MG (1978) Branched chain amino acid metabolism in the retina of diabetic rats. Diabetologia 14(3):171\u2013176","journal-title":"Diabetologia"},{"key":"5411_CR7","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/978-3-319-45096-4_5","volume":"13","author":"ME Conway","year":"2016","unstructured":"Conway ME, Hutson SM (2016) BCAA metabolism and NH(3) homeostasis. Adv Neurobiol 13:99\u2013132","journal-title":"Adv Neurobiol"},{"issue":"5","key":"5411_CR8","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1111\/1753-0407.12645","volume":"10","author":"Z Bloomgarden","year":"2018","unstructured":"Bloomgarden Z (2018) Diabetes and branched-chain amino acids: what is the link? J Diabetes 10(5):350\u2013352","journal-title":"J Diabetes"},{"issue":"2","key":"5411_CR9","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1111\/j.1471-4159.2011.07206.x","volume":"117","author":"K Gowda","year":"2011","unstructured":"Gowda K, Zinnanti WJ, LaNoue KF (2011) The influence of diabetes on glutamate metabolism in retinas. J Neurochem 117(2):309\u2013320","journal-title":"J Neurochem"},{"issue":"7","key":"5411_CR10","doi-asserted-by":"publisher","first-page":"2522","DOI":"10.1167\/iovs.04-1175","volume":"46","author":"M Tomi","year":"2005","unstructured":"Tomi M et al (2005) L-type amino acid transporter 1-mediated L-leucine transport at the inner blood-retinal barrier. Invest Ophthalmol Vis Sci 46(7):2522\u20132530","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"7","key":"5411_CR11","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1002\/jnr.23558","volume":"93","author":"J Hull","year":"2015","unstructured":"Hull J et al (2015) New insights into the role of the branched-chain aminotransferase proteins in the human brain. J Neurosci Res 93(7):987\u2013998","journal-title":"J Neurosci Res"},{"issue":"3","key":"5411_CR12","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1007\/s10522-020-09860-4","volume":"21","author":"ME Conway","year":"2020","unstructured":"Conway ME (2020) Alzheimer\u2019s disease: targeting the glutamatergic system. Biogerontology 21(3):257\u2013274","journal-title":"Biogerontology"},{"issue":"9","key":"5411_CR13","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1001\/archopht.1997.01100160331011","volume":"115","author":"J Ambati","year":"1997","unstructured":"Ambati J et al (1997) Elevated gamma-aminobutyric acid, glutamate, and vascular endothelial growth factor levels in the vitreous of patients with proliferative diabetic retinopathy. Arch Ophthalmol 115(9):1161\u20131166","journal-title":"Arch Ophthalmol"},{"key":"5411_CR14","doi-asserted-by":"publisher","DOI":"10.3390\/nu14204411","author":"I Ramzan","year":"2022","unstructured":"Ramzan I et al (2022) The association between circulating branched chain amino acids and the temporal risk of developing type 2 diabetes mellitus: a systematic review & meta-analysis. Nutrients. https:\/\/doi.org\/10.3390\/nu14204411","journal-title":"Nutrients"},{"issue":"2","key":"5411_CR15","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1007\/s00592-024-02349-3","volume":"62","author":"Q Gong","year":"2025","unstructured":"Gong Q et al (2025) Accumulation of branched-chain amino acids deteriorates the neuroinflammatory response of M\u00fcller cells in diabetic retinopathy via leucine\/Sestrin2-mediated sensing of mTOR signaling. Acta Diabetol 62(2):227\u2013240","journal-title":"Acta Diabetol"},{"key":"5411_CR16","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12186053","author":"DM Tanase","year":"2023","unstructured":"Tanase DM et al (2023) Depiction of branched-chain amino acids (BCAAs) in diabetes with a focus on diabetic microvascular complications. J Clin Med. https:\/\/doi.org\/10.3390\/jcm12186053","journal-title":"J Clin Med"},{"issue":"4","key":"5411_CR17","doi-asserted-by":"publisher","first-page":"303","DOI":"10.4103\/0976-500X.119726","volume":"4","author":"J Charan","year":"2013","unstructured":"Charan J, Kantharia ND (2013) How to calculate sample size in animal studies? J Pharmacol Pharmacother 4(4):303\u2013306","journal-title":"J Pharmacol Pharmacother"},{"issue":"6","key":"5411_CR18","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/nprot.2008.73","volume":"3","author":"TD Schmittgen","year":"2008","unstructured":"Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3(6):1101\u20131108","journal-title":"Nat Protoc"},{"key":"5411_CR19","first-page":"100916","volume":"25","author":"MH Shihan","year":"2021","unstructured":"Shihan MH et al (2021) A simple method for quantitating confocal fluorescent images. Biochem Biophys Rep 25:100916","journal-title":"Biochem Biophys Rep"},{"issue":"1","key":"5411_CR20","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/0003-2697(68)90092-4","volume":"25","author":"J Sedlak","year":"1968","unstructured":"Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman\u2019s reagent. Anal Biochem 25(1):192\u2013205","journal-title":"Anal Biochem"},{"issue":"1","key":"5411_CR21","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","volume":"193","author":"OH Lowry","year":"1951","unstructured":"Lowry OH et al (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265\u2013275","journal-title":"J Biol Chem"},{"key":"5411_CR22","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.preteyeres.2017.11.002","volume":"64","author":"JS Joyal","year":"2018","unstructured":"Joyal JS, Gantner ML, Smith LEH (2018) Retinal energy demands control vascular supply of the retina in development and disease: the role of neuronal lipid and glucose metabolism. Prog Retin Eye Res 64:131\u2013156","journal-title":"Prog Retin Eye Res"},{"issue":"5","key":"5411_CR23","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1111\/1753-0407.12639","volume":"10","author":"G Asghari","year":"2018","unstructured":"Asghari G et al (2018) High dietary intake of branched-chain amino acids is associated with an increased risk of insulin resistance in adults. J Diabetes 10(5):357\u2013364","journal-title":"J Diabetes"},{"issue":"3","key":"5411_CR24","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1007\/BF00283757","volume":"22","author":"P Vannini","year":"1982","unstructured":"Vannini P et al (1982) Branched-chain amino acids and alanine as indices of the metabolic control in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetic patients. Diabetologia 22(3):217\u2013219","journal-title":"Diabetologia"},{"key":"5411_CR25","doi-asserted-by":"crossref","unstructured":"Karusheva Y, Strassburger K, Markgraf DF, Zaharia OP, B\u00f3dis K, K\u00f6ssler T et al (2021) Branched-chain amino acids associate negatively with postprandial insulin secretion in recent-onset diabetes. J Endocr Soc 5(6):bvab067","DOI":"10.1210\/jendso\/bvab067"},{"key":"5411_CR26","doi-asserted-by":"publisher","DOI":"10.2337\/db19-533-P","author":"L-L Lim","year":"2019","unstructured":"Lim L-L et al (2019) 533-P: association of serum branched-chain amino acids with kidney function decline in type 2 diabetes: the Hong Kong Diabetes Register. Diabetes. https:\/\/doi.org\/10.2337\/db19-533-P","journal-title":"Diabetes"},{"issue":"10","key":"5411_CR27","doi-asserted-by":"publisher","first-page":"4948","DOI":"10.1111\/jcmm.13759","volume":"22","author":"O Zhenyukh","year":"2018","unstructured":"Zhenyukh O et al (2018) Branched-chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation. J Cell Mol Med 22(10):4948\u20134962","journal-title":"J Cell Mol Med"},{"issue":"6 Suppl","key":"5411_CR28","doi-asserted-by":"publisher","first-page":"1539s","DOI":"10.1093\/jn\/135.6.1539S","volume":"135","author":"JD Fernstrom","year":"2005","unstructured":"Fernstrom JD (2005) Branched-chain amino acids and brain function. J Nutr 135(6 Suppl):1539s-s1546","journal-title":"J Nutr"},{"issue":"3","key":"5411_CR29","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1142\/S0219635209002198","volume":"8","author":"S Hidaka","year":"2009","unstructured":"Hidaka S (2009) Serotonergic synapses modulate generation of spikes from retinal ganglion cells of teleosts. J Integr Neurosci 8(3):299\u2013322","journal-title":"J Integr Neurosci"},{"key":"5411_CR30","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.biochi.2018.11.006","volume":"161","author":"J Masson","year":"2019","unstructured":"Masson J (2019) Serotonin in retina. Biochimie 161:51\u201355","journal-title":"Biochimie"},{"issue":"2","key":"5411_CR31","doi-asserted-by":"publisher","first-page":"2559","DOI":"10.3390\/ijms14022559","volume":"14","author":"MS Ola","year":"2013","unstructured":"Ola MS et al (2013) Neurodegeneration and neuroprotection in diabetic retinopathy. Int J Mol Sci 14(2):2559\u20132572","journal-title":"Int J Mol Sci"},{"issue":"1","key":"5411_CR32","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1186\/s12886-020-01553-3","volume":"20","author":"Y Liu","year":"2020","unstructured":"Liu Y et al (2020) The expression and significance of mTORC1 in diabetic retinopathy. BMC Ophthalmol 20(1):297","journal-title":"BMC Ophthalmol"},{"key":"5411_CR33","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.973856","volume":"9","author":"F Casciano","year":"2022","unstructured":"Casciano F et al (2022) The role of the mTOR pathway in diabetic retinopathy. Front Med 9:973856","journal-title":"Front Med"},{"key":"5411_CR34","doi-asserted-by":"crossref","unstructured":"Aldosari DI et al (2024) Differential expression of branched-chain aminotransferase in the rat ocular tissues. J Histochem Cytochem 0(0): 00221554241272338","DOI":"10.1369\/00221554241272338"},{"issue":"6","key":"5411_CR35","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1111\/jnc.12044","volume":"123","author":"J Hull","year":"2012","unstructured":"Hull J et al (2012) Distribution of the branched chain aminotransferase proteins in the human brain and their role in glutamate regulation. J Neurochem 123(6):997\u20131009","journal-title":"J Neurochem"},{"issue":"6","key":"5411_CR36","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1007\/s11064-017-2261-5","volume":"42","author":"JE Sperringer","year":"2017","unstructured":"Sperringer JE, Addington A, Hutson SM (2017) Branched-chain amino acids and brain metabolism. Neurochem Res 42(6):1697\u20131709","journal-title":"Neurochem Res"},{"key":"5411_CR37","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.988290","volume":"12","author":"X Nong","year":"2022","unstructured":"Nong X et al (2022) The mechanism of branched-chain amino acid transferases in different diseases: research progress and future prospects. Front Oncol 12:988290","journal-title":"Front Oncol"},{"key":"5411_CR38","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23074022","author":"A Dimou","year":"2022","unstructured":"Dimou A, Tsimihodimos V, Bairaktari E (2022) The critical role of the branched chain amino acids (BCAAs) catabolism-regulating enzymes, branched-chain aminotransferase (BCAT) and branched-chain \u03b1-keto acid dehydrogenase (BCKD), in human pathophysiology. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms23074022","journal-title":"Int J Mol Sci"},{"issue":"2","key":"5411_CR39","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1111\/j.1460-9568.2004.03482.x","volume":"20","author":"F Madeddu","year":"2004","unstructured":"Madeddu F et al (2004) Intraocular delivery of BDNF following visual cortex lesion upregulates cytosolic branched chain aminotransferase (BCATc) in the rat dorsal lateral geniculate nucleus. Eur J Neurosci 20(2):580\u2013586","journal-title":"Eur J Neurosci"},{"issue":"3","key":"5411_CR40","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1007\/s10571-012-9901-8","volume":"33","author":"MS Ola","year":"2013","unstructured":"Ola MS et al (2013) Reduced levels of brain derived neurotrophic factor (BDNF) in the serum of diabetic retinopathy patients and in the retina of diabetic rats. Cell Mol Neurobiol 33(3):359\u2013367","journal-title":"Cell Mol Neurobiol"},{"issue":"1","key":"5411_CR41","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.brainres.2006.06.012","volume":"1108","author":"S Castellano","year":"2006","unstructured":"Castellano S et al (2006) Cytosolic branched chain aminotransferase (BCATc) mRNA is up-regulated in restricted brain areas of BDNF transgenic mice. Brain Res 1108(1):12\u201318","journal-title":"Brain Res"},{"key":"5411_CR42","first-page":"201","volume":"24","author":"R Natoli","year":"2018","unstructured":"Natoli R et al (2018) Obesity-induced metabolic disturbance drives oxidative stress and complement activation in the retinal environment. Mol Vis 24:201\u2013217","journal-title":"Mol Vis"},{"issue":"5","key":"5411_CR43","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1016\/j.bbadis.2013.02.001","volume":"1832","author":"R De Simone","year":"2013","unstructured":"De Simone R et al (2013) Branched-chain amino acids influence the immune properties of microglial cells and their responsiveness to pro-inflammatory signals. Biochim Biophys Acta 1832(5):650\u2013659","journal-title":"Biochim Biophys Acta"},{"issue":"6","key":"5411_CR44","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1006\/exer.2000.0840","volume":"70","author":"E Lieth","year":"2000","unstructured":"Lieth E et al (2000) Diabetes reduces glutamate oxidation and glutamine synthesis in the retina. The Penn State Retina Research Group. Exp Eye Res 70(6):723\u2013730","journal-title":"Exp Eye Res"},{"issue":"6","key":"5411_CR45","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1016\/j.exer.2009.08.006","volume":"89","author":"XH Yu","year":"2009","unstructured":"Yu XH et al (2009) Time-dependent reduction of glutamine synthetase in retina of diabetic rats. Exp Eye Res 89(6):967\u2013971","journal-title":"Exp Eye Res"},{"issue":"3","key":"5411_CR46","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1007\/s12035-014-8732-7","volume":"51","author":"V Jindal","year":"2015","unstructured":"Jindal V (2015) Neurodegeneration as a primary change and role of neuroprotection in diabetic retinopathy. Mol Neurobiol 51(3):878\u2013884","journal-title":"Mol Neurobiol"},{"issue":"42","key":"5411_CR47","doi-asserted-by":"publisher","first-page":"26438","DOI":"10.1073\/pnas.2009838117","volume":"117","author":"DE Mor","year":"2020","unstructured":"Mor DE et al (2020) Metformin rescues Parkinson\u2019s disease phenotypes caused by hyperactive mitochondria. Proc Natl Acad Sci U S A 117(42):26438\u201326447","journal-title":"Proc Natl Acad Sci U S A"},{"key":"5411_CR48","doi-asserted-by":"publisher","unstructured":"Yao V et al (2018) An integrative tissue-network approach to identify and test human disease genes. Nat Biotechnol. https:\/\/doi.org\/10.1038\/nbt.4246","DOI":"10.1038\/nbt.4246"},{"issue":"1","key":"5411_CR49","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s00395-021-00844-0","volume":"116","author":"Q Lai","year":"2021","unstructured":"Lai Q et al (2021) Oxoeicosanoid receptor inhibition alleviates acute myocardial infarction through activation of BCAT1. Basic Res Cardiol 116(1):3","journal-title":"Basic Res Cardiol"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-025-05411-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-025-05411-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-025-05411-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T11:16:36Z","timestamp":1764414996000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-025-05411-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,29]]},"references-count":49,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["5411"],"URL":"https:\/\/doi.org\/10.1007\/s12035-025-05411-5","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,29]]},"assertion":[{"value":"17 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"212"}}