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Invest Ophthalmol Vis Sci. 2017 Apr 1;58(4):2130-2138. doi: 10.1167/iovs.16-21094.

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

Author information

1
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.
2
Department of Ophthalmology, University of Erlangen-Nürnberg, Erlangen, Germany.
3
Iowa Lions Eye Bank, Coralville, Iowa, United States 3Cornea Research Center, University of Iowa, Iowa City, Iowa, United States.
4
University of Iowa College of Public Health, Department of Biostatistics, Iowa City, Iowa, United States.

Abstract

Purpose:

To characterize changes in the energy-producing metabolic activity and morphologic ultrastructure of corneal endothelial cells associated with diabetes mellitus.

Methods:

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).

Results:

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.

Conclusions:

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.

PMID:
28395029
DOI:
10.1167/iovs.16-21094
[Indexed for MEDLINE]

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