June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Altered protein expression in the diabetic human macula
Author Affiliations & Notes
  • Silke Becker
    Ophthalmology and Visual Sciences, University of Utah Health, Salt Lake City, Utah, United States
  • Frans Vinberg
    Ophthalmology and Visual Sciences, University of Utah Health, Salt Lake City, Utah, United States
  • Footnotes
    Commercial Relationships   Silke Becker None; Frans Vinberg None
  • Footnotes
    Support  Research was supported by an ARVO EyeFind Research Grant to SB and NEI R01 EY031706 and Research to Prevent Blindness/Dr. H. James and Carole Free Career Development Award to FV. The authors also acknowledge support from an RPB unrestricted grant to the Department of Ophthalmology at the University of Utah.
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 501. doi:
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      Silke Becker, Frans Vinberg; Altered protein expression in the diabetic human macula. Invest. Ophthalmol. Vis. Sci. 2023;64(8):501.

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

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Abstract

Purpose : Clinicians and scientists have long regarded diabetic retinopathy as a purely microvascular disease with areas of non-perfusion, microaneurysms, hemorrhages and neovascularization that can result in blindness. However, responses of retinal neurons to light are frequently altered in patients with diabetes and absence of light signaling protects mice with diabetes from vascular signs of diabetic retinopathy. The underlying mechanisms remain poorly understood specifically in the human macula, which is affected in diabetic macular edema. We evaluated whether chronic diabetes alters the expression of proteins in the human macula.

Methods : Eyes from 5 male diabetic donors (average age 83 ± 3 years) and 3 female and 1 male non-diabetic controls (average age 68 ± 12 years) were enucleated within 5 hours of death and transferred to the laboratory in Ames’ media. We measured the percentage of glycosylated hemoglobin (HbA1c) in blood samples and evaluated the trypsin-digested vascular networks of paraformaldehyde-fixed peripheral retinal punches. Using mass spectrometry we compared protein expression in TMT-labelled human maculas between donors with and without diabetes.

Results : Vascular networks from patients with diabetes ranged from normal appearance (HbA1c 5.4% and 6.5%) to reduced capillary density and microaneurysms (HbA1c 8.5 and 9.1%) and neovascularization (HbA1c 12.9%). Diabetes altered various pathways, most notably those associated with mitochondrial dysfunction, oxidative phosphorylation and glycolysis. The maculas of patients with diabetes contained more ATP synthase F1 subunit beta, NADH:ubiquinone oxidoreductase subunit A10, cytochrome-c oxidase subunit 7A2 and glyceraldehyde-3-phophate dehydrogenase, along with less NADH:ubiquinone oxidoreductase subunit A2 and ATP synthase membrane subunit c locus 1. Interestingly, the amounts of rhodopsin, G protein subunit gamma transducin 1 and G protein subunit alpha transducin 1 increased, while long wavelength sensitive Opsin 1, Arrestin 3 and Arrestin 1 decreased in diabetes.

Conclusions : Our study has identified a large number of proteins that diabetes altered in the maculas of patients with diabetes. Dysfunction of mitochondria and cellular energy metabolism represent frequent consequences of diabetes. Interestingly, our study also determined that diabetes modulates various light signal transmission proteins, which may contribute to altered light responses.

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

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