Mitochondrial and Morphologic Alterations in Native Human Corneal Endothelial Cells Associated With Diabetes Mellitus

Benjamin T Aldrich; Ursula Schlötzer-Schrehardt; Jessica M Skeie; Kimberlee A Burckart; Gregory A Schmidt; Cynthia R Reed; M Bridget Zimmerman; Friedrich E Kruse; Mark A Greiner

doi:10.1167/iovs.16-21094

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Mitochondrial and Morphologic Alterations in Native Human Corneal Endothelial Cells Associated With Diabetes Mellitus

Journal article

Open access

Peer reviewed

Mitochondrial and Morphologic Alterations in Native Human Corneal Endothelial Cells Associated With Diabetes Mellitus

Benjamin T Aldrich, Ursula Schlötzer-Schrehardt, Jessica M Skeie, Kimberlee A Burckart, Gregory A Schmidt, Cynthia R Reed, M Bridget Zimmerman, Friedrich E Kruse and Mark A Greiner

Investigative ophthalmology & visual science, Vol.58(4), pp.2130-2138

04/01/2017

DOI: 10.1167/iovs.16-21094

PMID: 28395029

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https://doi.org/10.1167/iovs.16-21094View

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Abstract

To characterize changes in the energy-producing metabolic activity and morphologic ultrastructure of corneal endothelial cells associated with diabetes mellitus. Transplant suitable corneoscleral tissue was obtained from donors aged 50 to 75 years. We assayed 3-mm punches of endothelium-Descemet membrane for mitochondrial respiration and glycolysis activity using extracellular flux analysis of oxygen and pH, respectively. Transmission electron microscopy was used to assess qualitative and quantitative ultrastructural changes in corneal endothelial cells and associated Descemet membrane. For purposes of analysis, samples were divided into four groups based on a medical history of diabetes regardless of type: (1) nondiabetic, (2) noninsulin-dependent diabetic, (3) insulin-dependent diabetic, and (4) insulin-dependent diabetic with specified complications due to diabetes (advanced diabetic). In total, 229 corneas from 159 donors were analyzed. Insulin-dependent diabetic samples with complications due to diabetes displayed the lowest spare respiratory values compared to all other groups (P ≤ 0.002). The remaining mitochondrial respiration and glycolysis metrics did not differ significantly among groups. Compared to nondiabetic controls, the endothelium from advanced diabetic samples had alterations in mitochondrial morphology, pronounced Golgi bodies associated with abundant vesicles, accumulation of lysosomal bodies/autophagosomes, and focal production of abnormal long-spacing collagen. Extracellular flux analysis suggests that corneal endothelial cells of donors with advanced diabetes have impaired mitochondrial function. Metabolic findings are supported by observed differences in mitochondrial morphology of advanced diabetic samples but not controls. Additional studies are needed to determine the precise mechanism(s) by which mitochondria become impaired in diabetic corneal endothelial cells.

Microscopy, Electron, Transmission

Descemet Membrane - metabolism

Cell Count

Corneal Diseases - etiology

Humans

Middle Aged

Diabetes Mellitus, Type 1 - pathology

Diabetes Mellitus, Type 1 - metabolism

Corneal Diseases - metabolism

Male

Mitochondria - metabolism

Diabetes Mellitus, Type 1 - complications

Endothelium, Corneal - ultrastructure

Mitochondria - ultrastructure

Descemet Membrane - ultrastructure

Oxygen - metabolism

Endothelium, Corneal - metabolism

Glycolysis - physiology

Cell Respiration - physiology

Female

Aged

Tissue Donors

Corneal Diseases - pathology

Details

Title: Subtitle: Mitochondrial and Morphologic Alterations in Native Human Corneal Endothelial Cells Associated With Diabetes Mellitus
Creators: Benjamin T Aldrich - University of Iowa Carver College of Medicine, Department of Ophthalmology and Visual Sciences, Iowa City, Iowa, United States 2Iowa Lions Eye Bank, Coralville, Iowa, United States 3Cornea Research Center, University of Iowa, Iowa City, Iowa, United States
Ursula Schlötzer-Schrehardt - Department of Ophthalmology, University of Erlangen-Nürnberg, Erlangen, Germany
Jessica M Skeie - University of Iowa Carver College of Medicine, Department of Ophthalmology and Visual Sciences, Iowa City, Iowa, United States 2Iowa Lions Eye Bank, Coralville, Iowa, United States 3Cornea Research Center, University of Iowa, Iowa City, Iowa, United States
Kimberlee A Burckart - Iowa Lions Eye Bank, Coralville, Iowa, United States 3Cornea Research Center, University of Iowa, Iowa City, Iowa, United States
Gregory A Schmidt - Iowa Lions Eye Bank, Coralville, Iowa, United States 3Cornea Research Center, University of Iowa, Iowa City, Iowa, United States
Cynthia R Reed - Iowa Lions Eye Bank, Coralville, Iowa, United States 3Cornea Research Center, University of Iowa, Iowa City, Iowa, United States
M Bridget Zimmerman - University of Iowa College of Public Health, Department of Biostatistics, Iowa City, Iowa, United States
Friedrich E Kruse - Department of Ophthalmology, University of Erlangen-Nürnberg, Erlangen, Germany
Mark A Greiner - University of Iowa Carver College of Medicine, Department of Ophthalmology and Visual Sciences, Iowa City, Iowa, United States 2Iowa Lions Eye Bank, Coralville, Iowa, United States 3Cornea Research Center, University of Iowa, Iowa City, Iowa, United States
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.58(4), pp.2130-2138
Publisher: United States
DOI: 10.1167/iovs.16-21094
PMID: 28395029
ISSN: 0146-0404
eISSN: 1552-5783
Language: English
Date published: 04/01/2017
Academic Unit: Biostatistics; Ophthalmology and Visual Sciences
Record Identifier: 9983979960702771

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