{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:00:51Z","timestamp":1791928851974,"version":"4.3.4"},"reference-count":69,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"5","license":[{"start":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T00:00:00Z","timestamp":1714953600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2024,5,6]]},"DOI":"10.1167\/iovs.65.5.11","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T13:01:28Z","timestamp":1716296488000},"page":"11","source":"Crossref","is-referenced-by-count":6,"title":["Impact of Obesity and Age on Mouse Corneal Innervation at the Epithelial-Stromal Interface"],"prefix":"10.1167","volume":"65","author":[{"given":"Justin A.","family":"Courson","sequence":"first","affiliation":[{"name":"Department of Medicine, Baylor College of Medicine, Houston, Texas, United States"},{"name":"Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolando E.","family":"Rumbaut","sequence":"additional","affiliation":[{"name":"Department of Medicine, Baylor College of Medicine, Houston, Texas, United States"},{"name":"Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan R.","family":"Burns","sequence":"additional","affiliation":[{"name":"College of Optometry, University of Houston, Houston, Texas, United States"},{"name":"Children's Nutrition Center, Baylor College of Medicine, Houston, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"190","DOI":"10.4103\/ijo.IJO_646_17","article-title":"Anatomy of cornea and ocular surface","volume":"66","author":"Sridhar","year":"2018","journal-title":"Indian J Ophthalmol"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/0304-3959(82)90092-6","article-title":"Density and organization of free nerve endings in the corneal epithelium of the rabbit","volume":"14","author":"Rozsa","year":"1982","journal-title":"Pain"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/S0014-4835(03)00050-2","article-title":"Corneal nerves: structure, contents and function","volume":"76","author":"Muller","year":"2003","journal-title":"Exp Eye Res"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"4695","DOI":"10.1167\/iovs.16-21372","article-title":"Corneal epithelium-derived neurotrophic factors promote nerve regeneration","volume":"58","author":"Di","year":"2017","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib5","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.4103\/1673-5374.213534","article-title":"Neurotrophic factors and corneal nerve regeneration","volume":"12","author":"Sacchetti","year":"2017","journal-title":"Neural Regen Res"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1136\/bjo.2006.112656","article-title":"Age-related differences in the normal human cornea: a laser scanning in vivo confocal microscopy study","volume":"91","author":"Niederer","year":"2007","journal-title":"Br J Ophthalmol"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.3109\/02713683.2015.1088952","article-title":"Age-related changes in murine corneal nerves","volume":"41","author":"Reichard","year":"2016","journal-title":"Curr Eye Res"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"e0224434","DOI":"10.1371\/journal.pone.0224434","article-title":"Serial block-face scanning electron microscopy reveals neuronal\u2013epithelial cell fusion in the mouse cornea","volume":"14","author":"Courson","year":"2019","journal-title":"PLoS One"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.jtos.2017.10.006","article-title":"The impact of diabetes on corneal nerve morphology and ocular surface integrity","volume":"16","author":"Markoulli","year":"2018","journal-title":"Ocul Surf"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"171","DOI":"10.3109\/08820538.2010.518133","article-title":"In vivo confocal microscopy of corneal nerves: analysis and clinical correlation","volume":"25","author":"Cruzat","year":"2010","journal-title":"Semin Ophthalmol"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.cveq.2004.04.014","article-title":"Corneal epithelial disease","volume":"20","author":"Cutler","year":"2004","journal-title":"Vet Clin North Am Equine Pract"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1016\/j.ajpath.2010.12.001","article-title":"IL-17 and VEGF are necessary for efficient corneal nerve regeneration","volume":"178","author":"Li","year":"2011","journal-title":"Am J Pathol"},{"key":"bib13","first-page":"240","article-title":"The influence of age on the sensitivity of the cornea","volume":"16","author":"Millodot","year":"1977","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.exer.2018.06.001","article-title":"High fat diet induces pre-type 2 diabetes with regional changes in corneal sensory nerves and altered P2X7 expression and localization","volume":"175","author":"Kneer","year":"2018","journal-title":"Exp Eye Res"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"e0238750","DOI":"10.1371\/journal.pone.0238750","article-title":"Corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity","volume":"15","author":"Hargrave","year":"2020","journal-title":"PLoS One"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"e12756","DOI":"10.1111\/jne.v32.1","article-title":"Sex differences in the peripubertal response to a short-term, high-fat diet intake","volume":"32","author":"Freire-Regatillo","year":"2020","journal-title":"J Neuroendocrinol"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.3389\/fphys.2018.01452","article-title":"Female mice have higher angiogenesis in perigonadal adipose tissue than males in response to high-fat diet","volume":"9","author":"Rudnicki","year":"2018","journal-title":"Front Physiol"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.yfrne.2017.05.003","article-title":"Sex differences in the neuroendocrine control of metabolism and the implication of astrocytes","volume":"48","author":"Chowen","year":"2018","journal-title":"Front Neuroendocrinol"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.mce.2014.11.029","article-title":"The sexual dimorphism of obesity","volume":"402","author":"Palmer","year":"2015","journal-title":"Mol Cell Endocrinol"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"2501","DOI":"10.1073\/pnas.0610787104","article-title":"Silencing of estrogen receptor alpha in the ventromedial nucleus of hypothalamus leads to metabolic syndrome","volume":"104","author":"Musatov","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"C1232","DOI":"10.1152\/ajpcell.00008.2006","article-title":"ICAM-1 expression in adipose tissue: effects of diet-induced obesity in mice","volume":"291","author":"Brake","year":"2006","journal-title":"Am J Physiol Cell Physiol"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"47585","DOI":"10.1074\/jbc.M305257200","article-title":"Standard isolation of primary adipose cells from mouse epididymal fat pads induces inflammatory mediators and down-regulates adipocyte genes","volume":"278","author":"Ruan","year":"2003","journal-title":"J Biol Chem"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1161\/ATVBAHA.109.198044","article-title":"CD11c expression in adipose tissue and blood and its role in diet-induced obesity","volume":"30","author":"Wu","year":"2010","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"e329","DOI":"10.1371\/journal.pbio.0020329","article-title":"Serial block-face scanning electron microscopy to reconstruct three-dimensional tissue nanostructure","volume":"2","author":"Denk","year":"2004","journal-title":"PLoS Biol"},{"key":"bib25","first-page":"e62045","article-title":"Serial block-face scanning electron microscopy (SBF-SEM) of biological tissue samples","author":"Courson","year":"2021","journal-title":"J Vis Exp"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"23721","DOI":"10.1038\/srep23721","article-title":"Conductive resins improve charging and resolution of acquired images in electron microscopic volume imaging","volume":"6","author":"Nguyen","year":"2016","journal-title":"Sci Rep"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"5023","DOI":"10.1167\/iovs.07-0562","article-title":"Neutrophil interactions with keratocytes during corneal epithelial wound healing: a role for CD18 integrins","volume":"48","author":"Petrescu","year":"2007","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1016\/j.exer.2010.08.007","article-title":"ICAM-1 mediates surface contact between neutrophils and keratocytes following corneal epithelial abrasion in the mouse","volume":"91","author":"Gagen","year":"2010","journal-title":"Exp Eye Res"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"e0182153","DOI":"10.1371\/journal.pone.0182153","article-title":"MyD88 contribution to ocular surface homeostasis","volume":"12","author":"Reins","year":"2017","journal-title":"PLoS One"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1038\/nrm2245","article-title":"Autophagy: from phenomenology to molecular understanding in less than a decade","volume":"8","author":"Klionsky","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.brainres.2016.03.047","article-title":"Mechanisms of neuronal homeostasis: autophagy in the axon","volume":"1649","author":"Maday","year":"2016","journal-title":"Brain Res"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"5933","DOI":"10.1523\/JNEUROSCI.4401-15.2016","article-title":"Compartment-specific regulation of autophagy in primary neurons","volume":"36","author":"Maday","year":"2016","journal-title":"J Neurosci"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1146\/physiol.1966.28.issue-1","article-title":"Functions of lysosomes","volume":"28","author":"De Duve","year":"1966","journal-title":"Annu Rev Physiol"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1083\/jcb.31.2.319","article-title":"Lysosome function in the regulation of the secretory process in cells of the anterior pituitary gland","volume":"31","author":"Smith","year":"1966","journal-title":"J Cell Biol"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.bj.2016.12.004","article-title":"From Christian de Duve to Yoshinori Ohsumi: more to autophagy than just dining at home","volume":"40","author":"Harnett","year":"2017","journal-title":"Biomed J"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.cell.2005.04.028","article-title":"Retrospective birth dating of cells in humans","volume":"122","author":"Spalding","year":"2005","journal-title":"Cell"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1146\/neuro.2014.37.issue-1","article-title":"Autophagy and its normal and pathogenic states in the brain","volume":"37","author":"Yamamoto","year":"2014","journal-title":"Annu Rev Neurosci"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"11","DOI":"10.4161\/auto.1.1.1513","article-title":"Autophagy and its possible roles in nervous system diseases, damage and repair","volume":"1","author":"Rubinsztein","year":"2005","journal-title":"Autophagy"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"591","DOI":"10.4161\/auto.4964","article-title":"Aberrant membranes and double-membrane structures accumulate in the axons of Atg5-null Purkinje cells before neuronal death","volume":"3","author":"Nishiyama","year":"2007","journal-title":"Autophagy"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"3907","DOI":"10.1128\/MCB.00627-13","article-title":"Autophagy negatively regulates early axon growth in cortical neurons","volume":"33","author":"Ban","year":"2013","journal-title":"Mol Cell Biol"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1083\/jcb.121.2.305","article-title":"Products of endocytosis and autophagy are retrieved from axons by regulated retrograde organelle transport","volume":"121","author":"Hollenbeck","year":"1993","journal-title":"J Cell Biol"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1083\/jcb.201412046","article-title":"Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes","volume":"209","author":"Cheng","year":"2015","journal-title":"J Cell Biol"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"359","DOI":"10.3390\/v9120359","article-title":"Autophagy in measles virus infection","volume":"9","author":"Rozi\u00e8res","year":"2017","journal-title":"Viruses"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"8527","DOI":"10.1128\/JVI.00807-12","article-title":"Membrane fusion-mediated autophagy induction enhances morbillivirus cell-to-cell spread","volume":"86","author":"Delpeut","year":"2012","journal-title":"J Virol"},{"key":"bib46","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1098\/rspb.1972.0040","article-title":"A light and electron microscopic study of the cellular response to axonal injury in the superior cervical ganglion of the rat","volume":"181","author":"Matthews","year":"1972","journal-title":"Proc R Soc Lond B Biol Sci"},{"key":"bib47","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1098\/rstb.1973.0002","article-title":"An ultrastructural study of axonal changes following constriction of postganglionic branches of the superior cervical ganglion in the rat","volume":"264","author":"Matthews","year":"1973","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"8057","DOI":"10.1523\/JNEUROSCI.2261-06.2006","article-title":"Induction of autophagy in axonal dystrophy and degeneration","volume":"26","author":"Wang","year":"2006","journal-title":"J Neurosci"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1083\/jcb.27.3.651","article-title":"Lysomes in the rat sciatic nerve following crush","volume":"27","author":"Holtzman","year":"1965","journal-title":"J Cell Biol"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"e44219","DOI":"10.7554\/eLife.44219","article-title":"Expression of WIPI2B counteracts age-related decline in autophagosome biogenesis in neurons","volume":"8","author":"Stavoe","year":"2019","journal-title":"eLife"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"107","DOI":"10.4161\/org.6.2.11687","article-title":"VEGF in the nervous system","volume":"6","author":"Rosenstein","year":"2010","journal-title":"Organogenesis"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.2337\/db10-0715","article-title":"Tumor progression locus 2 (TPL2) regulates obesity-associated inflammation and insulin resistance","volume":"60","author":"Perfield","year":"2011","journal-title":"Diabetes"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"14248","DOI":"10.1038\/s41598-018-32410-5","article-title":"Dendritic cell maturation in the corneal epithelium with onset of type 2 diabetes is associated with tumor necrosis factor receptor superfamily member 9","volume":"8","author":"Lagali","year":"2018","journal-title":"Sci Rep"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"3898","DOI":"10.1523\/JNEUROSCI.5225-11.2012","article-title":"In vivo nerve\u2013macrophage interactions following peripheral nerve injury","volume":"32","author":"Rosenberg","year":"2012","journal-title":"J Neurosci"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"36414","DOI":"10.1038\/srep36414","article-title":"Intraepithelial dendritic cells and sensory nerves are structurally associated and functional interdependent in the cornea","volume":"6","author":"Gao","year":"2016","journal-title":"Sci Rep"},{"issue":"suppl 1","key":"bib56","doi-asserted-by":"crossref","first-page":"S65","DOI":"10.1097\/ICO.0000000000000989","article-title":"Bilateral alterations in corneal nerves, dendritic cells, and tear cytokine levels in ocular surface disease","volume":"35","author":"Yamaguchi","year":"2016","journal-title":"Cornea"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"4369750","DOI":"10.1155\/2016\/4369750","article-title":"Corneal dendritic cell density is associated with subbasal nerve plexus features, ocular surface disease index, and serum vitamin D in evaporative dry eye disease","volume":"2016","author":"Shetty","year":"2016","journal-title":"Biomed Res Int"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s11357-016-9884-3","article-title":"Obesity and related consequences to ageing","volume":"38","author":"Jura","year":"2016","journal-title":"Age (Dordr)"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1016\/j.tig.2008.10.002","article-title":"Autophagy and aging: keeping that old broom working","volume":"24","author":"Cuervo","year":"2008","journal-title":"Trends Genet"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1007\/s00439-019-02031-7","article-title":"Autophagy in aging and longevity","volume":"139","author":"Wong","year":"2020","journal-title":"Human Genet"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/j.tcb.2011.06.008","article-title":"Taking a \u201cgood\u201d look at free radicals in the aging process","volume":"21","author":"Hekimi","year":"2011","journal-title":"Trends Cell Biol"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1167\/iovs.62.1.20","article-title":"Corneal keratocyte density and corneal nerves are reduced in patients with severe obesity and improve after bariatric surgery","volume":"62","author":"Iqbal","year":"2021","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1177\/1479164119826479","article-title":"Bariatric surgery as a model to explore the basis and consequences of the Reaven hypothesis: small, dense low-density lipoprotein and interleukin-6","volume":"16","author":"Adam","year":"2019","journal-title":"Diab Vasc Dis Res"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.3389\/fimmu.2017.01512","article-title":"Effect of Roux-en-Y bariatric surgery on lipoproteins, insulin resistance, and systemic and vascular inflammation in obesity and diabetes","volume":"8","author":"Yadav","year":"2017","journal-title":"Front Immunol"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/sj.ijo.0803418","article-title":"Prevalence of somatic small fiber neuropathy in obesity","volume":"31","author":"Herman","year":"2007","journal-title":"Int J Obes (Lond)"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1002\/ana.v74.3","article-title":"The metabolic syndrome and neuropathy: therapeutic challenges and opportunities","volume":"74","author":"Callaghan","year":"2013","journal-title":"Ann Neurol"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1016\/j.jdiacomp.2013.04.003","article-title":"Obesity and hyperlipidemia are risk factors for early diabetic neuropathy","volume":"27","author":"Smith","year":"2013","journal-title":"J Diabetes Complications"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1097\/SLA.0b013e3182a618b2","article-title":"Gastric bypass leads to improvement of diabetic neuropathy independent of glucose normalization\u2014results of a prospective cohort study (DiaSurg 1 study)","volume":"258","author":"M\u00fcller-Stich","year":"2013","journal-title":"Ann Surg"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"931","DOI":"10.3390\/ijms24020931","article-title":"A low-fat\/sucrose diet rich in complex carbohydrates reverses high-fat\/sucrose diet-induced corneal dysregulation","volume":"24","author":"Akowuah","year":"2023","journal-title":"Int J Mol Sci"},{"key":"bib29","volume-title":"Unbiased Stereology","author":"Howard","year":"2005","edition":"2nd ed"}],"container-title":["Investigative Ophthalmology & Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2793637","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:31:46Z","timestamp":1791927106000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2793637"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,6]]},"references-count":69,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.65.5.11","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2024,5,6]]}}}