June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Metabolic indications of diabetes progression in human aqueous humor
Author Affiliations & Notes
  • Christopher Fortenbach
    Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Jessica Marie Skeie
    Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States
    Iowa Lions Eye Bank, Coralville, Iowa, United States
  • Darryl Nashimura
    Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States
    Iowa Lions Eye Bank, Coralville, Iowa, United States
  • Mark A Greiner
    Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States
    Iowa Lions Eye Bank, Coralville, Iowa, United States
  • Footnotes
    Commercial Relationships   Christopher Fortenbach, None; Jessica Skeie, None; Darryl Nashimura, None; Mark Greiner, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 5013. doi:
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      Christopher Fortenbach, Jessica Marie Skeie, Darryl Nashimura, Mark A Greiner; Metabolic indications of diabetes progression in human aqueous humor. Invest. Ophthalmol. Vis. Sci. 2020;61(7):5013.

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

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Abstract

Purpose : Diabetes mellitus poses a significant threat to ocular health and vision. While the retina is widely recognized as a target of damage, diabetes also impacts the anterior segment and may result in diabetic patients requiring more frequent corneal and glaucoma surgeries. We hypothesize that the systemic metabolic derangement observed in the progression of diabetes also influences the composition of the aqueous humor (AH), which ultimately impacts anterior segment health. In order to identify metabolic changes associated with diabetes progression, we mapped the metabolite profile of AH samples of patients with varying severity of type II diabetes (T2DM).

Methods : Patients were classified as nondiabetic (control), non-insulin-dependent diabetic without advanced features of disease (NAD-ni), insulin-dependent diabetic without advanced features (NAD-i), or diabetic with advanced features (AD). AH samples were collected during anterior segment surgeries and frozen immediately. Metabolites were identified by GC-MS (Thermo Q Exactive GC). Data were collected in the full mass range (50-700 Da) and identification of metabolites was based on comparison with in-house standards and their retention times using Tracefinder 4.1 (Thermo Fisher). Metabolic pathway analysis was then conducted utilizing MetaboAnalyst 4.0 (MetaboAnalyst).

Results : A total of 12 control, 15 NAD-ni, 3 NAD-i, and 12 AD samples were included for analysis. AH samples from diabetic patients across severities demonstrated differences in various metabolites compared to control patients. Elevated levels of several carbohydrates including glucose (> 1.45 fold; p < 0.024) and fructose (> 1.41 fold; p < 0.025) were detected at all diabetic severities. Other metabolites, such as lysine (1.23 fold; p = 0.24), alanine (1.42 fold; p = 0.00013), and malate (1.29 fold; p = 0.022) were elevated relative to controls only in AD samples. These findings were mirrored in metabolic pathway analysis, which showed altered carbohydrate metabolism among all diabetic groups while amino acid biosynthesis changes were impacted by diabetes severity.

Conclusions : Diabetes results in metabolic perturbations detectable in the AH, and unique changes in substrate metabolism become manifest as T2DM severity worsens. Changes in AH composition may serve as an indicator of disease severity and risk assessment of anterior segment cells and structures.

This is a 2020 ARVO Annual Meeting abstract.

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