Ocular SurfacePub Date : 2024-10-01DOI: 10.1016/j.jtos.2024.09.005
{"title":"Metabolomics of basal tears in amyotrophic lateral sclerosis: A cross-sectional study","authors":"","doi":"10.1016/j.jtos.2024.09.005","DOIUrl":"10.1016/j.jtos.2024.09.005","url":null,"abstract":"<div><h3>Purpose</h3><div>Amyotrophic lateral sclerosis (ALS) clinical variability, along with the lack of conclusive diagnostic instruments, result in average diagnosis delays of 9 months. This study aimed to assess whether metabolomic profiling of basal tears in ALS patients could act as a biological marker for diagnosing ALS, predicting prognosis, and discriminating between endophenotypes.</div></div><div><h3>Methods</h3><div>A single-center prospective case-control study was conducted in France from September 2021 to March 2023 including patients with ALS according to the revised EI Escorial criteria. Two microliters of basal tears were collected using microcapillary glass tubes and analyzed with ultra-high performance liquid chromatography coupled with mass spectrometry. Both univariate and multivariate analyses were performed.</div></div><div><h3>Results</h3><div>Twenty-five patients with ALS and 30 controls were included. No significant differences in metabolite levels were found between ALS and control groups (p > 0.05). The basal tear metabolome significantly discriminated bulbar and spinal forms of ALS based on 6 metabolites, among which 5 were decreased (aniline, trigonelline, caffeine, theophylline and methyl beta-D-galactoside) in the bulbar form and 1 was decreased in the spinal form (dodecanedioic acid).</div></div><div><h3>Conclusion</h3><div>This study represents the first prospective analysis of basal tear metabolomics in individuals with ALS. Despite the inability to distinguish between ALS patients and controls based on metabolic signatures, these findings could contribute to understanding the phenotypic diversity of ALS. Notably, distinct metabolic profiles were identified that differentiate between the bulbar and spinal forms of the disease.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ocular SurfacePub Date : 2024-09-19DOI: 10.1016/j.jtos.2024.09.003
{"title":"Changes in conjunctival mononuclear phagocytes and suppressive activity of regulatory macrophages in desiccation induced dry eye","authors":"","doi":"10.1016/j.jtos.2024.09.003","DOIUrl":"10.1016/j.jtos.2024.09.003","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the effects of dry eye on conjunctival immune cell number and transcriptional profiles with attention to mononuclear phagocytes.</div></div><div><h3>Methods</h3><div>Expression profiling was performed by single-cell RNA sequencing on sorted conjunctival immune cells from non-stressed and C57BL/6 mice subjected to desiccating stress (DS). Monocle 3 modeled cell trajectory, scATAC-seq assessed chromatin accessibility and IPA identified canonical pathways. Inflammation and goblet cells were measured after depletion of MRC1<sup>+</sup> MΦs with mannosylated clodronate liposomes.</div></div><div><h3>Results</h3><div>Mononuclear phagocytes (monocytes, MΦs, DCs) comprised 72 % of immune cells and showed the greatest changes with DS. Distinct DS induced gene expression patterns were seen in phagocytes classified by expression of Ccr2 and [Timd4, Lyve1, Folr2 (TLR)]. Expression of phagocytosis/efferocytosis genes increased in TLF<sup>+</sup>CCR2<sup>-</sup> MΦs. Monocytes showed the highest expression of Ace, Cx3cr1, Vegfa, Ifngr1,2, and Stat1 and TLF<sup>−</sup>CCR2<sup>+</sup> cells expressed higher levels of inflammatory mediators (Il1a, Il1b, Il1rn, Nfkb1, Ccl5, MHCII, Cd80, Cxcl10, Icam1). A trajectory from monocyte precursors branched to terminate in regulatory MΦs or in mDCs via transitional MΦ and cDC clusters. Activated pathways in TLF<sup>+</sup> cells include phagocytosis, PPAR/RXRα activation, IL-10 signaling, alternate MΦ activation, while inflammatory pathways were suppressed. Depletion of MRC1<sup>+</sup> MΦs increased IL-17 and IFN-γ expression and cytokine-expressing T cells, reduced IL-10 and worsened goblet loss.</div></div><div><h3>Conclusions</h3><div>Dryness stimulates distinct gene expression patterns in conjunctival phagocytes, increasing expression of regulatory genes in TLF<sup>+</sup> cells regulated in part by RXRα, and inflammatory genes in CCR2<sup>+</sup> cells. Regulatory MΦs depletion worsens DS induced inflammation and goblet cell loss.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142305335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ocular SurfacePub Date : 2024-09-12DOI: 10.1016/j.jtos.2024.09.002
{"title":"Epidemiology and risk factors for the development of cicatrizing conjunctivitis in chronic ocular graft-versus-host disease","authors":"","doi":"10.1016/j.jtos.2024.09.002","DOIUrl":"10.1016/j.jtos.2024.09.002","url":null,"abstract":"<div><h3>Purpose</h3><p>To evaluate the incidence of chronic cicatrizing conjunctivitis (CCC) and its associated risk factors in the context of chronic ocular graft-vs-host disease (coGVHD).</p></div><div><h3>Methods</h3><p>A retrospective chart review of individuals diagnosed with coGVHD following hematopoietic stem cell transplantation (HSCT) who were seen at the Bascom Palmer Eye Institute between May 2010 and November 2021 was performed. Data regarding baseline demographic characteristics, systemic co-morbidities, lid margin abnormalities, ocular cicatricial changes, transplant information, immunosuppressive therapy, and GVHD severity assessments were collected. The incidence of cicatricial conjunctivitis was estimated with Kaplan-Meier survival analysis. A Cox regression model was used to assess the contribution of demographic and systemic variables to the development of CCC.</p></div><div><h3>Results</h3><p>167 individuals were included (53.9 ± 14.7 years old; 60.5 % male). 65 individuals presented with features suggestive of CCC an average of 60.9 ± 53.8 months after HSCT, with 60-month and 120-month incidences of 29.3 % and 48.9 %, respectively. Multivariable analysis demonstrated that age younger than 50 at the time of the first eye visit was associated with a higher chance of CCC development (Hazard Ratio (HR): 2.14, 95 % Confidence Interval (CI): 1.16–3.97, p = 0.02).</p></div><div><h3>Conclusion</h3><p>Clinically detected cicatrizing conjunctivitis is an ocular manifestation of coGVHD, with an incidence that increases over time. Younger individuals may be at higher risk for CCC development.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ocular SurfacePub Date : 2024-08-31DOI: 10.1016/j.jtos.2024.08.016
{"title":"Detection of SARS-CoV-2 binding receptors and miscellaneous targets as well as mucosal surface area of the human lacrimal drainage system","authors":"","doi":"10.1016/j.jtos.2024.08.016","DOIUrl":"10.1016/j.jtos.2024.08.016","url":null,"abstract":"<div><h3>Purpose</h3><p>Our aim was to evaluate a potential role for the lacrimal drainage system (LDS) as a portal of entry and conduit for SARS-CoV-2 in human infection. We also investigate the mucosal surface area. The relatively long tear contact time in a closed system raises the possibility that this pathway may contribute to the initiation of systemic infection. We looked for expression of ACE2, the main receptor for SARS-CoV-2, as well as cofactors such as TMPRSS2 and other enzymes such as cathepsinB, CD147, elastase1, furin, neuropilin1, neuropilin2, TMPRSS11D and trypsin which also play a role in SARS-CoV-2 infection, in this system.</p></div><div><h3>Methods</h3><p>Human tissue samples of the draining tear ducts from body donors were analyzed by RT-PCR, Western blot and immunohistochemistry. It is not known whether the respective body donors were Sars-Cov-2 positive at any time; they were negative when they entered the institute. Besides, the draining LDS of body donors were measured to determine the mucosal surface in the lacrimal system.</p></div><div><h3>Results</h3><p>The expression of the main receptor studied, ACE2, cofactors such as TMPRSS2 and other enzymes such as cathepsinB, CD147, elastase1, furin, neuropilin1, neuropilin2, TMPRSS11D and trypsin were all detected at the gene and protein level. The average mucosal surface area of the lacrimal sac and nasolacrimal duct was calculated to be 110 mm<sup>2</sup>.</p></div><div><h3>Conclusion</h3><p>The results show the presence of all analyzed receptors in the efferent LDS. With an average tear passage time of 3 min and a relatively large mucosal surface area, the LDS could therefore be considered as a portal of entry and conduit for SARS-CoV-2. In addition, it represents a surface that should be taken into consideration in the administration of topically applied medication to the ocular surface.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S154201242400096X/pdfft?md5=077e26d0d5c1c1c911787a4ebc91c667&pid=1-s2.0-S154201242400096X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ocular SurfacePub Date : 2024-08-30DOI: 10.1016/j.jtos.2024.08.013
{"title":"Readership awareness series – Paper 13: Key concepts of translational research","authors":"","doi":"10.1016/j.jtos.2024.08.013","DOIUrl":"10.1016/j.jtos.2024.08.013","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ocular SurfacePub Date : 2024-08-29DOI: 10.1016/j.jtos.2024.08.015
{"title":"Development and characterization of a preclinical mouse model of alkali-induced limbal stem cell deficiency","authors":"","doi":"10.1016/j.jtos.2024.08.015","DOIUrl":"10.1016/j.jtos.2024.08.015","url":null,"abstract":"<div><h3>Purpose</h3><p>Limbal stem cell deficiency (LSCD) secondary to ocular surface alkali burn is a blinding condition that features corneal conjunctivalization. Mechanistic insights into its pathophysiology are lacking. Here, we developed a mouse model that recapitulates human disease to comprehensively delineate the clinicopathological features of a conjunctivalized cornea.</p></div><div><h3>Methods</h3><p>LSCD was induced in the right eyes of 6-8-week-old C57BL/6 male and female mice (<em>n = 151</em>) by topical administration of 0.25N sodium hydroxide on the cornea. Uninjured left eyes served as controls. Clinical, histological, phenotypic, molecular, and immunological assessments were performed at multiple time-points over 6-months.</p></div><div><h3>Results</h3><p>Clinically, alkali burn caused persistent corneal opacity (p = 0.0014), increased punctate staining (p = 0.0002), and reduced epithelial thickness (p = 0.0082) compared to controls. Total LSCD was confirmed in corneal whole mounts by loss of K12 protein (p < 0.0001) and mRNA expression (p = 0.0090). Instead, K8<sup>+</sup>, K13<sup>+</sup>, K15<sup>+</sup> and MUC5AC<sup>+</sup> conjunctival epithelia prevailed. 20 % of injured corneas developed islands of K12<sup>+</sup> epithelia, suggesting epithelial transdifferentiation. Squamous metaplasia was detected in 50 % of injured corneas. Goblet cell density peaked early post-injury but decreased over time (p = 0.0047). Intraepithelial corneal basal nerve density remained reduced even at 6-months post-injury (p = 0.0487).</p></div><div><h3>Conclusions</h3><p>We developed and comprehensively characterized a preclinical mouse model of alkali-induced LSCD. Understanding the pathophysiological processes that transpire on the ocular surface in LSCD is key to discovering, testing, and advancing biological and pharmacological interventions that can be dispensed prior to or in conjunction with stem cell therapy to rehabilitate the cornea and restore vision.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1542012424000958/pdfft?md5=592d460a11f75adc137bf2afe15e6ac6&pid=1-s2.0-S1542012424000958-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ocular SurfacePub Date : 2024-08-28DOI: 10.1016/j.jtos.2024.08.014
{"title":"Distinctive small molecules blend: Promotes lacrimal gland epithelial cell proliferation in vitro and accelerates lacrimal gland injury repair in vivo","authors":"","doi":"10.1016/j.jtos.2024.08.014","DOIUrl":"10.1016/j.jtos.2024.08.014","url":null,"abstract":"<div><h3>Purpose</h3><p>This study aims to develop a novel serum-free culture strategy containing only two small molecules, Y27632 and SB431542 (2C), for <em>in vitro</em> expansion of mouse lacrimal gland epithelial cells (LGECs) and investigate an innovative therapeutic approach for lacrimal gland (LG) injury.</p></div><div><h3>Methods</h3><p>LGECs proliferative capacity was assessed by cell counting, crystal violet staining, qRT-PCR and immunofluorescence. Cell differentiation was achieved by manipulating culture conditions and assessed by qRT-PCR and AQP5 immunofluorescence. LGECs were seeded in Matrigel for three-dimensional culture and assessed by qRT-PCR and immunofluorescence. Secretory function of the cultures was assayed by ELISA. <em>In vivo</em>, 2C injection verified its reparative capacity in a mouse LG injury model. Corneal fluorescein staining, phenol red cotton thread, H&E, immunofluorescence and Western blot were used to assess LG injury repair.</p></div><div><h3>Results</h3><p>LGECs cultured with 2C exhibited high expression of stemness/proliferation markers and maintained morphology and proliferative capacity even after the tenth passage. Removal of 2C was efficacious in achieving LGECs differentiation, characterized by the increased AQP5 expression and LTF secretion. 3D spheroids cultured with 2C demonstrated differentiation potential, forming microglandular structures containing multiple LG cell types with secretory functions after 2C removal. <em>In vivo</em>, 2C improved the structural integrity and function of the injured LG.</p></div><div><h3>Conclusions</h3><p>We present a small molecule combination, 2C, that promotes LGECs expansion and differentiation <em>in vitro</em> and accelerates LG injury repair <em>in vivo</em>. This approach has potential applications for providing a stable source of seed cells for tissue engineering applications, providing new sights for LG-related diseases treatment.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142099513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ocular SurfacePub Date : 2024-08-26DOI: 10.1016/j.jtos.2024.08.012
{"title":"β-Catenin gain of function mutant in mouse periocular neural crest-derived mesenchymal cells impairs embryonic eyelid morphogenesis and leads to blepharophimosis syndrome in mice","authors":"","doi":"10.1016/j.jtos.2024.08.012","DOIUrl":"10.1016/j.jtos.2024.08.012","url":null,"abstract":"<div><h3>Purpose</h3><p>The aberrant canonical Wnt-β-catenin signaling can cause devastating outcomes of tissue morphogenesis and tumor formation. In this study, we examined the impact of overexpression of constitutive active β-catenin in mouse periocular neural crest-derived mesenchymal cells during embryonic eyelid morphogenesis.</p></div><div><h3>Methods</h3><p>We expressed a stabilized β-catenin in which the exon 3 of the <em>Ctnnb</em>1 gene was deleted in periocular neural crest (PONC)-derived eyelid stromal cells (<em>Ctnnb1</em><sup><em>Δex3-PONC</em></sup>). Histopathological examinations were performed to examine the eyelid morphogenetic alterations in <em>Ctnnb1</em><sup><em>Δex3-PONC</em></sup> mice. Immunohistochemical investigations for cell proliferation, apoptosis, and differentiation were also assessed.</p></div><div><h3>Results</h3><p>We discovered that nuclear accumulation of β-catenin resulted in a reduction of nuclear Ki-67 and phospho-Erk1/2 expression levels and elevation of apoptosis in PONC cells during embryonic eyelid closure morphogenesis. Interestingly, however, the eyelid epithelial migration was not affected, which resulted in only eyelid epidermal closure but lacked underneath dermal formation at embryonic (E) day 16.5. The sequelae of <em>Ctnnb1</em><sup><em>Δex3-PONC</em></sup> revealed the malformation of the eyelid margin and Meibomian gland and deficiency of Muller's smooth muscle fibers formation. Consequently, <em>Ctnnb1</em><sup><em>Δex3-PONC</em></sup> mice manifested blepharophimosis syndrome at P21.</p></div><div><h3>Conclusion</h3><p>Our data suggested that aberrant expression of β-catenin gain of function in PONC interrupts the interplay between epithelium and stroma for the morphogenesis of eyelid closure during embryonic development.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142087227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ocular SurfacePub Date : 2024-08-17DOI: 10.1016/j.jtos.2024.08.009
{"title":"Serum-derived extracellular vesicles for the treatment of severe ocular surface disease","authors":"","doi":"10.1016/j.jtos.2024.08.009","DOIUrl":"10.1016/j.jtos.2024.08.009","url":null,"abstract":"<div><h3>Purpose</h3><p>Autologous serum is widely used for the treatment of severe ocular surface disease with mixed efficacy. Extracellular vesicles (EVs) are small membrane bound structures present in all body fluids, including serum. This study compared the proteomic, metabolomic, and inflammatory cytokine composition of serum-derived EVs (SDEVs) to that of the soluble free protein fraction and the subsequent capacity of SDEVs to induce corneal epithelial cell migration and inflammation.</p></div><div><h3>Methods</h3><p>SDEVs were isolated from human serum using size exclusion chromatography. SDEVs were analyzed using nanoparticle tracking analysis, transmission electron microscopy, and western blotting. The effects of SDEVs on corneal epithelial cell migration were tested using a standard scratch assay. Inflammatory cytokines in SDEVs and the free protein fraction were quantified using a microarray. A mutli-omics approach was further used to define SDEV cargo. The ability of SDEVs to modulate inflammation in corneal epithelial cells was quantified using ELISAs.</p></div><div><h3>Results</h3><p>Western blot and TEM confirmed the presence of SDEVs. Proinflammatory cytokines, along with complement proteins and TGF-β, were decreased in SDEVs compared to serum. Metabolites present in SDEVs were mostly involved in amino acid biosynthesis, the TCA cycle and oxidative phosphorylation. SDEVs exhibited pro-migratory effects similar to serum however, SDEVs did not induce secretion of IL-6 or IL-8.</p></div><div><h3>Conclusions</h3><p>SDEVs exhibit reduced levels of pro-inflammatory cytokines while retaining the beneficial wound healing properties of serum. Unlike serum, SDEVs do not induce inflammation. SDEVs may represent an alternative option for patients with severe ocular surface disease where traditional autologous serum has failed.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ocular SurfacePub Date : 2024-08-15DOI: 10.1016/j.jtos.2024.08.011
{"title":"Tear neuropeptide Y as a non-invasive marker of peripheral microvascular complications in type 1 diabetes","authors":"","doi":"10.1016/j.jtos.2024.08.011","DOIUrl":"10.1016/j.jtos.2024.08.011","url":null,"abstract":"<div><h3>Aims</h3><p>To investigate tear neuropeptide Y (NPY) and substance P concentrations in individuals with type 1 diabetes, comparing those with and without both diabetic retinopathy (DR) and peripheral neuropathy.</p></div><div><h3>Methods</h3><p>This cross-sectional study involved 41 participants with type 1 diabetes and none to moderate DR, and 22 healthy controls. Assessments included clinical ocular surface parameters, quantification of corneal nerve attributes (based on <em>in vivo</em> confocal microscopy imaging), DR grading, and evaluation for small and large fibre neuropathy. Concentrations of NPY and substance P in tear samples were measured using enzyme-linked immunosorbent assay.</p></div><div><h3>Results</h3><p>Mean (± standard deviation) tear NPY concentrations in participants with type 1 diabetes and length-dependent small fibre neuropathy (SFN) was lower than in controls (10.84 ± 4.10 ng/mL vs 14.72 ± 3.12 ng/mL; <em>p=</em>0.004), but not significantly different from type 1 diabetes participants without SFN (13.39 ± 4.66 ng/mL; <em>p=</em>0.11). Tear NPY levels were lower in individuals with type 1 diabetes and mild/moderate non-proliferative DR (10.44 ± 3.46 ng/mL) compared to none/minimal DR (13.79 ± 4.76 ng/mL; <em>p=</em>0.0005) and controls. In separate linear regression models, both the presence of SFN (β = −0.75, <em>p=</em>0.02) and the presence of mild/moderate DR (β = −0.84, <em>p=</em>0.009) were significantly associated with tear NPY levels relative to controls, after adjusting for participant age, sex, and dry eye disease. There were no inter-group differences for tear substance P concentrations.</p></div><div><h3>Conclusions</h3><p>Tear NPY has potential utility as an indicator of peripheral microvascular complications associated with type 1 diabetes.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}