{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:04:26Z","timestamp":1793149466135,"version":"4.5.0"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:00:00Z","timestamp":1698969600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:00:00Z","timestamp":1698969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["511337830"],"award-info":[{"award-number":["511337830"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["512541541"],"award-info":[{"award-number":["512541541"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medizinische Fakult\u00e4t Mannheim der Universit\u00e4t Heidelberg"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Caveolin-1 (Cav-1) is a pivotal protein in the plasma membrane. Studies on homozygous Cav-1 deficient mice revealed that Cav-1 is essential for endothelial function and angiogenesis in the retina. However, whether a reduction in Cav-1 content hampers the neurovascular unit\u00a0(NVU) in the retina is unclear. Thus, this study examines the NVU in the retinas of heterozygous Cav-1 deficient (Cav-1<jats:sup>+\/\u2212<\/jats:sup>) mice and analyzes possible underlying mechanisms.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The vascular, glial and neuronal components in the retina were evaluated using retinal morphometry, whole mount retinal immunofluorescence staining, histological analysis and optical coherence tomography. In addition, immunoblotting and immunofluorescence staining, subcellular fractionation, biotin labeling of cell surface proteins, and proximity ligation assay were employed to detect expression and localization of proteins in the retina or endothelial cells (ECs) upon knockdown of Cav-1 with Cav-1 siRNA.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Cav-1<jats:sup>+\/\u2212<\/jats:sup> retinas showed a significant reduction in pericyte coverage along with an increase in acellular capillaries compared to controls at 8\u00a0months of age, but not at 1\u00a0month. A significant loss and obvious morphological abnormalities of smooth muscle cells were observed in 8-month-old Cav-1<jats:sup>+\/\u2212<\/jats:sup> retinal arterioles. Macroglial and microglial cells were activated in the Cav-1<jats:sup>+\/\u2212<\/jats:sup> retinas. A transient significant delay in retinal angiogenesis was detected in Cav-1<jats:sup>+\/\u2212<\/jats:sup> retinas at p5, which was however no longer detectable at p10. The Cav-1<jats:sup>+\/\u2212<\/jats:sup> retinas displayed increased vascular permeability and a notable reduction in VEGFR2 content at 8\u00a0months. In vitro, siRNA-mediated knockdown experiments in ECs revealed that the loss of Cav-1 in ECs resulted in decreased levels of VEGFR2, VE-Cadherin and their interaction at the plasma membrane as well.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our results indicate that a sufficient Cav-1 level over 50% of its normal abundance is vital for the proper localization of VEGFR2 and VE-cadherin, likely in a complex, at the plasma membrane, which is essential for the maintenance of normal NVU in the retina.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s10020-023-00749-9","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T10:02:35Z","timestamp":1699005755000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sufficient Cav-1 levels in the endothelium are critical for the maintenance of the neurovascular unit in the retina"],"prefix":"10.1186","volume":"29","author":[{"given":"Yixin","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Halawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupriya","family":"Chatterjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachana","family":"Eshwaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohanes Cakrapradipta","family":"Wibowo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyuan","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Wieland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5680-5142","authenticated-orcid":false,"given":"Yuxi","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,3]]},"reference":[{"issue":"4","key":"749_CR1","doi-asserted-by":"publisher","first-page":"908","DOI":"10.2337\/db16-0586","volume":"66","author":"C Andre","year":"2017","unstructured":"Andre C, et al. Inhibiting microglia expansion prevents diet-induced hypothalamic and peripheral inflammation. Diabetes. 2017;66(4):908\u201319.","journal-title":"Diabetes"},{"issue":"6","key":"749_CR2","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1016\/j.cell.2019.01.021","volume":"176","author":"RS Apte","year":"2019","unstructured":"Apte RS, Chen DS, Ferrara N. VEGF in signaling and disease: beyond discovery and development. Cell. 2019;176(6):1248\u201364.","journal-title":"Cell"},{"issue":"7","key":"749_CR3","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1161\/01.RES.0000125295.43813.1F","volume":"94","author":"F Baffert","year":"2004","unstructured":"Baffert F, et al. Age-related changes in vascular endothelial growth factor dependency and angiopoietin-1-induced plasticity of adult blood vessels. Circ Res. 2004;94(7):984\u201392.","journal-title":"Circ Res"},{"issue":"4","key":"749_CR4","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.preteyeres.2006.05.003","volume":"25","author":"A Bringmann","year":"2006","unstructured":"Bringmann A, et al. M\u00fcller cells in the healthy and diseased retina. Prog Retin Eye Res. 2006;25(4):397\u2013424.","journal-title":"Prog Retin Eye Res"},{"issue":"6","key":"749_CR5","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1038\/nm0603-653","volume":"9","author":"P Carmeliet","year":"2003","unstructured":"Carmeliet P. Angiogenesis in health and disease. Nat Med. 2003;9(6):653\u201360.","journal-title":"Nat Med"},{"issue":"7070","key":"749_CR6","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1038\/nature04478","volume":"438","author":"P Carmeliet","year":"2005","unstructured":"Carmeliet P. Angiogenesis in life, disease and medicine. Nature. 2005;438(7070):932\u20136.","journal-title":"Nature"},{"issue":"4","key":"749_CR7","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.2353\/ajpath.2009.090171","volume":"175","author":"SH Chang","year":"2009","unstructured":"Chang SH, et al. Vascular permeability and pathological angiogenesis in caveolin-1-null mice. Am J Pathol. 2009;175(4):1768\u201376.","journal-title":"Am J Pathol"},{"issue":"4","key":"749_CR8","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.molmed.2020.11.006","volume":"27","author":"L Claesson-Welsh","year":"2021","unstructured":"Claesson-Welsh L, Dejana E, McDonald DM. Permeability of the endothelial barrier: identifying and reconciling controversies. Trends Mol Med. 2021;27(4):314\u201331.","journal-title":"Trends Mol Med"},{"issue":"4","key":"749_CR9","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1152\/physrev.00046.2003","volume":"84","author":"AW Cohen","year":"2004","unstructured":"Cohen AW, et al. Role of caveolae and caveolins in health and disease. Physiol Rev. 2004;84(4):1341\u201379.","journal-title":"Physiol Rev"},{"issue":"2","key":"749_CR10","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/S0002-9394(99)00323-2","volume":"129","author":"MK Davidson","year":"2000","unstructured":"Davidson MK, et al. Reduced expression of the adherens junction protein cadherin-5 in a diabetic retina. Am J Ophthalmol. 2000;129(2):267\u20139.","journal-title":"Am J Ophthalmol"},{"issue":"5539","key":"749_CR11","doi-asserted-by":"publisher","first-page":"2449","DOI":"10.1126\/science.1062688","volume":"293","author":"M Drab","year":"2001","unstructured":"Drab M, et al. Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice. Science. 2001;293(5539):2449\u201352.","journal-title":"Science"},{"issue":"4","key":"749_CR12","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1167\/tvst.4.4.9","volume":"4","author":"C Dysli","year":"2015","unstructured":"Dysli C, et al. quantitative analysis of mouse retinal layers using automated segmentation of spectral domain optical coherence tomography images. Transl vis Sci Technol. 2015;4(4):9.","journal-title":"Transl vis Sci Technol"},{"key":"749_CR13","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2022.101094","volume":"91","author":"EN Enyong","year":"2022","unstructured":"Enyong EN, et al. Caveolar and non-Caveolar Caveolin-1 in ocular homeostasis and disease. Prog Retin Eye Res. 2022;91: 101094.","journal-title":"Prog Retin Eye Res"},{"key":"749_CR14","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2021.101333","volume":"54","author":"R Eshwaran","year":"2021","unstructured":"Eshwaran R, et al. Glucosamine protects against neuronal but not vascular damage in experimental diabetic retinopathy. Mol Metab. 2021;54: 101333.","journal-title":"Mol Metab"},{"issue":"1","key":"749_CR15","first-page":"157","volume":"40","author":"Y Feng","year":"1999","unstructured":"Feng Y, et al. VEGF-induced permeability increase is mediated by caveolae. Invest Ophthalmol vis Sci. 1999;40(1):157\u201367.","journal-title":"Invest Ophthalmol vis Sci"},{"issue":"1\u20133","key":"749_CR16","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1159\/000113755","volume":"21","author":"Y Feng","year":"2008","unstructured":"Feng Y, et al. Angiopoietin-2 deficiency decelerates age-dependent vascular changes in the mouse retina. Cell Physiol Biochem. 2008;21(1\u20133):129\u201336.","journal-title":"Cell Physiol Biochem"},{"issue":"2","key":"749_CR17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016865","volume":"6","author":"Y Feng","year":"2011","unstructured":"Feng Y, et al. Gene expression profiling of vasoregression in the retina\u2013involvement of microglial cells. PLoS ONE. 2011;6(2): e16865.","journal-title":"PLoS ONE"},{"issue":"6","key":"749_CR18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067265","volume":"8","author":"LR Ferguson","year":"2013","unstructured":"Ferguson LR, et al. Retinal thickness normative data in wild-type mice using customized miniature SD-OCT. PLoS ONE. 2013;8(6): e67265.","journal-title":"PLoS ONE"},{"issue":"7070","key":"749_CR19","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1038\/nature04482","volume":"438","author":"RF Gariano","year":"2005","unstructured":"Gariano RF, Gardner TW. Retinal angiogenesis in development and disease. Nature. 2005;438(7070):960\u20136.","journal-title":"Nature"},{"issue":"7","key":"749_CR20","doi-asserted-by":"publisher","first-page":"2471","DOI":"10.1177\/0271678X16669365","volume":"37","author":"S Gross","year":"2017","unstructured":"Gross S, et al. Nucleoside diphosphate kinase B regulates angiogenic responses in the endothelium via caveolae formation and c-Src-mediated caveolin-1 phosphorylation. J Cereb Blood Flow Metab. 2017;37(7):2471\u201384.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"2","key":"749_CR21","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.ajpath.2013.10.022","volume":"184","author":"X Gu","year":"2014","unstructured":"Gu X, et al. Loss of caveolin-1 causes blood-retinal barrier breakdown, venous enlargement, and mural cell alteration. Am J Pathol. 2014a;184(2):541\u201355.","journal-title":"Am J Pathol"},{"key":"749_CR22","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/978-1-4614-3209-8_3","volume":"801","author":"X Gu","year":"2014","unstructured":"Gu X, et al. Spatial and temporal localization of caveolin-1 protein in the developing retina. Adv Exp Med Biol. 2014b;801:15\u201321.","journal-title":"Adv Exp Med Biol"},{"key":"749_CR23","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.1038\/ncomms2683","volume":"4","author":"M Hayashi","year":"2013","unstructured":"Hayashi M, et al. VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation. Nat Commun. 2013;4:1672.","journal-title":"Nat Commun"},{"issue":"2","key":"749_CR24","doi-asserted-by":"publisher","first-page":"101","DOI":"10.4142\/jvs.2006.7.2.101","volume":"7","author":"H Kim","year":"2006","unstructured":"Kim H, et al. Immunohistochemical study of caveolin-1 and -2 in the rat retina. J Vet Sci. 2006;7(2):101\u20134.","journal-title":"J Vet Sci"},{"issue":"1","key":"749_CR25","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.exer.2009.01.006","volume":"89","author":"I Klaassen","year":"2009","unstructured":"Klaassen I, et al. Altered expression of genes related to blood-retina barrier disruption in streptozotocin-induced diabetes. Exp Eye Res. 2009;89(1):4\u201315.","journal-title":"Exp Eye Res"},{"issue":"1","key":"749_CR26","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1091\/mbc.e02-07-0379","volume":"14","author":"L Labrecque","year":"2003","unstructured":"Labrecque L, et al. Regulation of vascular endothelial growth factor receptor-2 activity by caveolin-1 and plasma membrane cholesterol. Mol Biol Cell. 2003;14(1):334\u201347.","journal-title":"Mol Biol Cell"},{"issue":"20","key":"749_CR27","doi-asserted-by":"publisher","first-page":"16424","DOI":"10.1074\/jbc.M112.353763","volume":"287","author":"X Li","year":"2012","unstructured":"Li X, et al. Loss of caveolin-1 impairs retinal function due to disturbance of subretinal microenvironment. J Biol Chem. 2012;287(20):16424\u201334.","journal-title":"J Biol Chem"},{"issue":"6","key":"749_CR28","doi-asserted-by":"publisher","first-page":"2849","DOI":"10.1158\/0008-5472.CAN-06-4082","volume":"67","author":"MI Lin","year":"2007","unstructured":"Lin MI, et al. Caveolin-1-deficient mice have increased tumor microvascular permeability, angiogenesis, and growth. Cancer Res. 2007;67(6):2849\u201356.","journal-title":"Cancer Res"},{"issue":"11","key":"749_CR29","doi-asserted-by":"publisher","first-page":"6202","DOI":"10.3390\/ijms23116202","volume":"23","author":"C Lin","year":"2022","unstructured":"Lin C, et al. Myopia alters the structural organization of the retinal vasculature, gfap-positive glia, and ganglion cell layer thickness. Int J Mol Sci. 2022;23(11):6202.","journal-title":"Int J Mol Sci"},{"issue":"6","key":"749_CR30","doi-asserted-by":"publisher","first-page":"L1179","DOI":"10.1152\/ajplung.00242.2003","volume":"285","author":"RD Minshall","year":"2003","unstructured":"Minshall RD, et al. Caveolin regulation of endothelial function. Am J Physiol Lung Cell Mol Physiol. 2003;285(6):L1179\u201383.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"2","key":"749_CR31","doi-asserted-by":"publisher","first-page":"L405","DOI":"10.1152\/ajplung.00292.2005","volume":"290","author":"K Miyawaki-Shimizu","year":"2006","unstructured":"Miyawaki-Shimizu K, et al. siRNA-induced caveolin-1 knockdown in mice increases lung vascular permeability via the junctional pathway. Am J Physiol Lung Cell Mol Physiol. 2006;290(2):L405\u201313.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"6","key":"749_CR32","doi-asserted-by":"publisher","first-page":"3784","DOI":"10.1167\/iovs.10-6386","volume":"52","author":"S Rangasamy","year":"2011","unstructured":"Rangasamy S, et al. A potential role for angiopoietin 2 in the regulation of the blood-retinal barrier in diabetic retinopathy. Invest Ophthalmol vis Sci. 2011;52(6):3784\u201391.","journal-title":"Invest Ophthalmol vis Sci"},{"issue":"41","key":"749_CR33","doi-asserted-by":"publisher","first-page":"38121","DOI":"10.1074\/jbc.M105408200","volume":"276","author":"B Razani","year":"2001","unstructured":"Razani B, et al. Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J Biol Chem. 2001;276(41):38121\u201338.","journal-title":"J Biol Chem"},{"key":"749_CR34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neurobiolaging.2018.06.039","volume":"71","author":"AM Reagan","year":"2018","unstructured":"Reagan AM, et al. Age-related focal loss of contractile vascular smooth muscle cells in retinal arterioles is accelerated by caveolin-1 deficiency. Neurobiol Aging. 2018;71:1\u201312.","journal-title":"Neurobiol Aging"},{"issue":"5","key":"749_CR35","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1002\/glia.22477","volume":"61","author":"A Reichenbach","year":"2013","unstructured":"Reichenbach A, Bringmann A. New functions of M\u00fcller cells. Glia. 2013;61(5):651\u201378.","journal-title":"Glia"},{"key":"749_CR36","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.3389\/fnins.2019.01172","volume":"13","author":"MG Rossino","year":"2019","unstructured":"Rossino MG, Dal Monte M, Casini G. Relationships between neurodegeneration and vascular damage in diabetic retinopathy. Front Neurosci. 2019;13:1172.","journal-title":"Front Neurosci"},{"issue":"11","key":"749_CR37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003554","volume":"3","author":"M Saint-Geniez","year":"2008","unstructured":"Saint-Geniez M, et al. Endogenous VEGF is required for visual function: evidence for a survival role on muller cells and photoreceptors. PLoS ONE. 2008;3(11): e3554.","journal-title":"PLoS ONE"},{"issue":"42","key":"749_CR38","doi-asserted-by":"publisher","first-page":"40091","DOI":"10.1074\/jbc.M205948200","volume":"277","author":"W Schubert","year":"2002","unstructured":"Schubert W, et al. Microvascular hyperpermeability in caveolin-1 (-\/-) knock-out mice. Treatment with a specific nitric-oxide synthase inhibitor, L-NAME, restores normal microvascular permeability in Cav-1 null mice. J Biol Chem. 2002;277(42):40091\u20138.","journal-title":"J Biol Chem"},{"issue":"6535","key":"749_CR39","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/376062a0","volume":"376","author":"F Shalaby","year":"1995","unstructured":"Shalaby F, et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature. 1995;376(6535):62\u20136.","journal-title":"Nature"},{"key":"749_CR40","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.54056","author":"RO Smith","year":"2020","unstructured":"Smith RO, et al. Vascular permeability in retinopathy is regulated by VEGFR2 Y949 signaling to VE-cadherin. Elife. 2020. https:\/\/doi.org\/10.7554\/eLife.54056.","journal-title":"Elife"},{"key":"749_CR41","doi-asserted-by":"publisher","first-page":"120","DOI":"10.3389\/fphys.2011.00120","volume":"2","author":"G Sowa","year":"2012","unstructured":"Sowa G. Caveolae, caveolins, cavins, and endothelial cell function: new insights. Front Physiol. 2012;2:120.","journal-title":"Front Physiol"},{"issue":"23","key":"749_CR42","doi-asserted-by":"publisher","first-page":"2286","DOI":"10.4161\/cbt.8.23.10138","volume":"8","author":"SA Tahir","year":"2009","unstructured":"Tahir SA, Park S, Thompson TC. Caveolin-1 regulates VEGF-stimulated angiogenic activities in prostate cancer and endothelial cells. Cancer Biol Ther. 2009;8(23):2286\u201396.","journal-title":"Cancer Biol Ther"},{"issue":"1","key":"749_CR43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053220","volume":"8","author":"A Tarradas","year":"2013","unstructured":"Tarradas A, et al. A novel missense mutation, I890T, in the pore region of cardiac sodium channel causes Brugada syndrome. PLoS ONE. 2013;8(1): e53220.","journal-title":"PLoS ONE"},{"issue":"2","key":"749_CR44","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1161\/ATVBAHA.107.158014","volume":"28","author":"D Vestweber","year":"2008","unstructured":"Vestweber D. VE-cadherin: the major endothelial adhesion molecule controlling cellular junctions and blood vessel formation. Arterioscler Thromb Vasc Biol. 2008;28(2):223\u201332.","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"1","key":"749_CR45","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/S0306-4522(02)00374-3","volume":"115","author":"D Virgintino","year":"2002","unstructured":"Virgintino D, et al. Expression of caveolin-1 in human brain microvessels. Neuroscience. 2002;115(1):145\u201352.","journal-title":"Neuroscience"},{"issue":"4","key":"749_CR46","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.tins.2012.11.007","volume":"36","author":"H Wake","year":"2013","unstructured":"Wake H, et al. Microglia: actively surveying and shaping neuronal circuit structure and function. Trends Neurosci. 2013;36(4):209\u201317.","journal-title":"Trends Neurosci"},{"issue":"5","key":"749_CR47","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1007\/s00592-014-0616-9","volume":"51","author":"J Wang","year":"2014","unstructured":"Wang J, et al. CD74 indicates microglial activation in experimental diabetic retinopathy and exogenous methylglyoxal mimics the response in normoglycemic retina. Acta Diabetol. 2014;51(5):813\u201321.","journal-title":"Acta Diabetol"},{"issue":"17","key":"749_CR48","doi-asserted-by":"publisher","first-page":"11375","DOI":"10.1073\/pnas.172360799","volume":"99","author":"YY Zhao","year":"2002","unstructured":"Zhao YY, et al. Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice. Proc Natl Acad Sci U S A. 2002;99(17):11375\u201380.","journal-title":"Proc Natl Acad Sci U S A"}],"container-title":["Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10020-023-00749-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s10020-023-00749-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10020-023-00749-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T11:09:44Z","timestamp":1699009784000},"score":1,"resource":{"primary":{"URL":"https:\/\/molmed.biomedcentral.com\/articles\/10.1186\/s10020-023-00749-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,3]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["749"],"URL":"https:\/\/doi.org\/10.1186\/s10020-023-00749-9","relation":{},"ISSN":["1528-3658"],"issn-type":[{"value":"1528-3658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,3]]},"assertion":[{"value":"26 June 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 October 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Animal care and experiments were conducted in accordance with institutional guidelines and in compliance with the Association for Research in Vision and Ophthalmology statement. The study was approved by the Medical Faculty Mannheim, Heidelberg University, Germany.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The manuscript has been approved for submission by the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The author(s) have declared no potential conflicts of interest with respect to the research, authorship, and\/or publication of this article.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"152"}}