June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Diabetes-related Hyperglycemia Affects Protein Expression and Glycation Events in the Extracellular Matrix of Corneal Endothelial Cells
Author Affiliations & Notes
  • Kenten Kingsbury
    Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
    Iowa Lions Eye Bank, Coralville, Iowa, United States
  • Jessica M. Skeie
    Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
    Iowa Lions Eye Bank, Coralville, Iowa, United States
  • Tim Eggleston
    Iowa Lions Eye Bank, Coralville, Iowa, United States
  • Hanna Shevalye
    Iowa Lions Eye Bank, Coralville, Iowa, United States
  • Greg Schmidt
    Iowa Lions Eye Bank, Coralville, Iowa, United States
  • Esther Baker
    Iowa Lions Eye Bank, Coralville, Iowa, United States
  • Mark A Greiner
    Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
    Iowa Lions Eye Bank, Coralville, Iowa, United States
  • Footnotes
    Commercial Relationships   Kenten Kingsbury None; Jessica Skeie None; Tim Eggleston None; Hanna Shevalye None; Greg Schmidt None; Esther Baker None; Mark Greiner None
  • Footnotes
    Support  Eye Bank Association of America Pilot Research Grant
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 660. doi:
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      Kenten Kingsbury, Jessica M. Skeie, Tim Eggleston, Hanna Shevalye, Greg Schmidt, Esther Baker, Mark A Greiner; Diabetes-related Hyperglycemia Affects Protein Expression and Glycation Events in the Extracellular Matrix of Corneal Endothelial Cells. Invest. Ophthalmol. Vis. Sci. 2023;64(8):660.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Many aspects of healthcare are affected by the high prevalence of diabetes mellitus, including corneal tissue transplantation. Previous work has demonstrated that there are protein expression changes in the extracellular matrix of corneal endothelial cells (CECs) secondary to diabetes. Further, corneal tissues from diabetic donors tear more frequently during graft preparation for Descemet membrane (DM) endothelial keratoplasty and may have reduced graft survival. It is unclear how microscopic protein expression changes and mechanical differences seen clinically are connected to diabetes severity. We set out to isolate hyperglycemia as one aspect of diabetes to understand how these alterations directly may correspond to observed changes. Specifically, we wanted to investigate if a controlled hyperglycemic environment could initiate protein expression changes associated with clinically observed graft insufficiencies.

Methods : Immortalized human CECs were cultured in 4 states of increasing hyperglycemia. Cell and DM protein fractions were isolated separately. Donor cornea tissues were grouped by diabetes severity, including non-diabetic controls (n=5) and non-insulin dependent (n=5) and insulin dependent (n=4) diabetic tissues. CEC and DM protein fractions were isolated separately. Samples were analyzed via immunohistochemistry and western blot assays.

Results : In CEC and DM fractions, western blotting results showed increases in TGFBI and advanced glycation end products (AGEs) were correlated with increasing hyperglycemia. TGFBI expression was highest in DM fractions of insulin-dependent diabetic donor tissues, whereas vitronectin was highest in the non-insulin dependent diabetic tissues. With immunohistochemistry, increased TGFBI and AGEs were seen with increasing hyperglycemia and were colocalized. Fibronectin signal was most intense in the highest hyperglycemic environment.

Conclusions : Diabetes-related hyperglycemia alters the extracellular matrix of CECs by initiating changes in protein expression and increased AGE deposition. Findings suggest that irreversible corneal tissue damage associated with graft tearing and failure may be related to extracellular protein modifications secondary to hyperglycemia.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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