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The effect of high-fat diet-induced metabolic disturbance on corneal neuroimmune features.
Exp Eye Res. 2020 12; 201:108298.EE

Abstract

PURPOSE

The highly innervated cornea is susceptible to nerve loss secondary to systemic diseases such as diabetes and metabolic disturbances caused by high-fat diet. In this study, we characterize the effect of high-fat diet on the mouse corneal neuroimmune phenotype, including changes to corneal nerve density and resident immune cells, alongside the clinical assessment of corneal thickness and endothelial cell density.

METHODS

Male C57Bl6/J mice, aged 10 weeks, were fed a high-fat diet (60 kcal% fat, 5.2 kcal/g) or control diet (10 kcal%, 3.8 kcal/g) for 16 weeks. At the study endpoint, metabolic parameters (HbA1c, weight, fasting glucose, body fat) were measured to confirm metabolic disturbance. Clinical imaging of the anterior segment was performed using optical coherence tomography to measure the corneal epithelial and stromal thickness. Corneal sensory nerves were visualized using flatmount immunostaining and confocal microscopy. The topographical distribution and density of sensory nerves (BIII-tubulin+), intraepithelial CD45+ and MHC- II+ cells, stromal macrophages (IBA1+CD206+) and endothelial cells (ZO-1+) were analysed using FIJI.

RESULTS

High-fat diet mice had significantly higher blood HbA1c, higher body weight, a higher percentage of body fat and elevated fasting glucose compared to the control diet mice. Corneal epithelial and stromal thickness was similar in both groups. The sum length of the basal nerve plexus was lower in the central and peripheral cornea of mice fed a high-fat diet. In contrast, the sum length of superficial nerve terminals was similar between groups. Epithelial immune cell density was two-fold higher in the central corneas of high-fat diet mice compared to control diet mice. IBA1+CD206+ macrophage density was similar in the anterior stroma of both groups but was significantly higher in the posterior stroma of the peripheral cornea in the high-fat diet mice compared to controls. The percentage of nerve-associated MHC-II+ cells in the epithelium and stroma was higher in HFD mice compared to controls. Endothelial cell density was similar in the corneas of high-fat diet mice compared to controls.

CONCLUSION

Together with corneal neuropathy, corneal immune cells in mice fed a high-fat diet were differentially affected depending on their topographical distribution and location within cornea, and appeared in closer proximity to epithelial and stromal nerves, suggesting a local neuroimmune disruption induced by systemic metabolic disturbance.

Authors+Show Affiliations

Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, Australia.Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, Australia.Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, Victoria, Australia.Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Department of Medicine, Western Health, Melbourne University, Sunshine, Victoria, Australia.Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, Victoria, Australia; Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, Australia. Electronic address: holly.chinnery@unimelb.edu.au.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33069696

Citation

Jiao, Haihan, et al. "The Effect of High-fat Diet-induced Metabolic Disturbance On Corneal Neuroimmune Features." Experimental Eye Research, vol. 201, 2020, p. 108298.
Jiao H, Lim AS, Fazio Coles TE, et al. The effect of high-fat diet-induced metabolic disturbance on corneal neuroimmune features. Exp Eye Res. 2020;201:108298.
Jiao, H., Lim, A. S., Fazio Coles, T. E., McQuade, R. M., Furness, J. B., & Chinnery, H. R. (2020). The effect of high-fat diet-induced metabolic disturbance on corneal neuroimmune features. Experimental Eye Research, 201, 108298. https://doi.org/10.1016/j.exer.2020.108298
Jiao H, et al. The Effect of High-fat Diet-induced Metabolic Disturbance On Corneal Neuroimmune Features. Exp Eye Res. 2020;201:108298. PubMed PMID: 33069696.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of high-fat diet-induced metabolic disturbance on corneal neuroimmune features. AU - Jiao,Haihan, AU - Lim,Alicia Sl, AU - Fazio Coles,Therese E, AU - McQuade,Rachel M, AU - Furness,John B, AU - Chinnery,Holly R, Y1 - 2020/10/15/ PY - 2020/04/29/received PY - 2020/10/07/revised PY - 2020/10/09/accepted PY - 2020/10/19/pubmed PY - 2021/3/2/medline PY - 2020/10/18/entrez KW - Cornea KW - Corneal intraepithelial immune cells KW - High-fat diet KW - Macrophages KW - Sensory nerves SP - 108298 EP - 108298 JF - Experimental eye research JO - Exp Eye Res VL - 201 N2 - PURPOSE: The highly innervated cornea is susceptible to nerve loss secondary to systemic diseases such as diabetes and metabolic disturbances caused by high-fat diet. In this study, we characterize the effect of high-fat diet on the mouse corneal neuroimmune phenotype, including changes to corneal nerve density and resident immune cells, alongside the clinical assessment of corneal thickness and endothelial cell density. METHODS: Male C57Bl6/J mice, aged 10 weeks, were fed a high-fat diet (60 kcal% fat, 5.2 kcal/g) or control diet (10 kcal%, 3.8 kcal/g) for 16 weeks. At the study endpoint, metabolic parameters (HbA1c, weight, fasting glucose, body fat) were measured to confirm metabolic disturbance. Clinical imaging of the anterior segment was performed using optical coherence tomography to measure the corneal epithelial and stromal thickness. Corneal sensory nerves were visualized using flatmount immunostaining and confocal microscopy. The topographical distribution and density of sensory nerves (BIII-tubulin+), intraepithelial CD45+ and MHC- II+ cells, stromal macrophages (IBA1+CD206+) and endothelial cells (ZO-1+) were analysed using FIJI. RESULTS: High-fat diet mice had significantly higher blood HbA1c, higher body weight, a higher percentage of body fat and elevated fasting glucose compared to the control diet mice. Corneal epithelial and stromal thickness was similar in both groups. The sum length of the basal nerve plexus was lower in the central and peripheral cornea of mice fed a high-fat diet. In contrast, the sum length of superficial nerve terminals was similar between groups. Epithelial immune cell density was two-fold higher in the central corneas of high-fat diet mice compared to control diet mice. IBA1+CD206+ macrophage density was similar in the anterior stroma of both groups but was significantly higher in the posterior stroma of the peripheral cornea in the high-fat diet mice compared to controls. The percentage of nerve-associated MHC-II+ cells in the epithelium and stroma was higher in HFD mice compared to controls. Endothelial cell density was similar in the corneas of high-fat diet mice compared to controls. CONCLUSION: Together with corneal neuropathy, corneal immune cells in mice fed a high-fat diet were differentially affected depending on their topographical distribution and location within cornea, and appeared in closer proximity to epithelial and stromal nerves, suggesting a local neuroimmune disruption induced by systemic metabolic disturbance. SN - 1096-0007 UR - https://www.unboundmedicine.com/medline/citation/33069696/The_effect_of_high_fat_diet_induced_metabolic_disturbance_on_corneal_neuroimmune_features_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(20)30556-X DB - PRIME DP - Unbound Medicine ER -