Type II Diabetes Mellitus Causes Extracellular Matrix Alterations in the Posterior Cornea That Increase Graft Thickness and Rigidity

Kingsbury KD, Skeie JM, Cosert K, Schmidt GA, Aldrich BT, Sales CS, Weller J, Kruse F, Thomasy SM, Schlötzer-Schrehardt U, Greiner MA (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Investigative Ophthalmology & Visual Science Association for Research in Vision and Ophthalmology (ARVO)

Book Volume: 64

Article Number: 26

Journal Issue: 7

DOI: 10.1167/iovs.64.7.26

Abstract

PURPOSE. There is a pressing need to investigate the impact of type II diabetes mellitus on the posterior cornea in donor tissues given its increasing prevalence and potential impact on endothelial keratoplasty surgical outcomes. METHODS. Immortalized human cultured corneal endothelial cells (CECs; HCEC-B4G12) were grown in hyperglycemic media for 2 weeks. Extracellular matrix (ECM) adhesive glycoprotein expression and advanced glycation end products (AGEs) in cultured cells and corneoscleral donor tissues, as well as the elastic modulus for the Descemet membrane (DMs) and CECs of diabetic and nondiabetic donor corneas, were measured. RESULTS. In CEC cultures, increasing hyperglycemia resulted in increased transforming growth factor beta-induced (TGFBI) protein expression and colocalization with AGEs in the ECM. In donor corneas, the thicknesses of the DM and the interfacial matrix (IFM) between the DM and stroma both increased from 8.42 ± 1.35 μm and 0.504 ± 0.13 μm in normal corneas, respectively, to 11.13 ± 2.91 μm (DM) and 0.681 ± 0.24 μm (IFM) in non-advanced diabetes (P = 0.013 and P = 0.075, respectively) and 11.31 ± 1.76 μm (DM) and 0.744 ± 0.18 μm (IFM) in advanced diabetes (AD; P = 0.0002 and P = 0.003, respectively). Immunofluorescence in AD tissues versus controls showed increased AGEs (P < 0.001) and markedly increased labeling intensity for adhesive glycoproteins, including TGFBI, that colocalized with AGEs. The elastic modulus significantly increased between AD and control tissues for the DMs (P < 0.0001) and CECs (P < 0.0001). CONCLUSIONS. Diabetes and hyperglycemia alter human CEC ECM structure and composition, likely contributing to previously documented complications of endothelial keratoplasty using diabetic donor tissue, including tearing during graft preparation and reduced graft survival. AGE accumulation in the DM and IFM may be a useful biomarker for determining diabetic impact on posterior corneal tissue.

Authors with CRIS profile

Julia Weller Medizinische Fakultät Friedrich Kruse Lehrstuhl für Augenheilkunde Ursula Schlötzer-Schrehardt Medizinische Fakultät

Involved external institutions

University of Iowa US United States (USA) (US) University of California Davis (UCDAVIS) US United States (USA) (US)

How to cite

APA:

Kingsbury, K.D., Skeie, J.M., Cosert, K., Schmidt, G.A., Aldrich, B.T., Sales, C.S.,... Greiner, M.A. (2023). Type II Diabetes Mellitus Causes Extracellular Matrix Alterations in the Posterior Cornea That Increase Graft Thickness and Rigidity. Investigative Ophthalmology & Visual Science, 64(7). https://dx.doi.org/10.1167/iovs.64.7.26

MLA:

Kingsbury, Kenten D., et al. "Type II Diabetes Mellitus Causes Extracellular Matrix Alterations in the Posterior Cornea That Increase Graft Thickness and Rigidity." Investigative Ophthalmology & Visual Science 64.7 (2023).

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