In:
PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 1 ( 2023-1-18), p. e0280491-
Abstract:
Diabetes mellitus is a multiorgan systemic disease impacting numerous ocular structures that results in significant ocular morbidity and often results in more frequent corneal and glaucoma surgeries for affected individuals. We hypothesize that the systemic metabolic and proteomic derangement observed in the progression of diabetes influences the composition of the aqueous humor (AH), which ultimately impacts the anterior segment health of the eye. To identify changes associated with diabetes progression, we mapped the metabolite profile and proteome of AH samples from patients with varying severities of type II diabetes (T2DM). Patients were classified as nondiabetic (ND or 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 collected from the anterior chamber during elective ophthalmic surgery were evaluated for metabolite and protein expression changes associated with diabetic severity via gas chromatography/mass spectrometry and ultra-high performance liquid chromatography tandem mass spectrometry, respectively. Metabolic and proteomic pathway analyses were conducted utilizing MetaboAnalyst 4.0 and Ingenuity Pathway Analysis. A total of 14 control, 12 NAD-ni, 4 NAD-I, and 14 AD samples were included for analysis. Elevated levels of several branched amino acids (e.g., valine, leucine, isoleucine), and lipid metabolites (e.g., palmitate) were found only with increasing diabetic severity (i.e., the AD group). Similar proteomic trends were noted in amino acid and fatty acid metabolism and the unfolded protein/stress response. These results represent the first report of both metabolomic and proteomic evaluation of aqueous humor. Diabetes results in metabolic and proteomic perturbations detectable in the AH, and unique changes become manifest as T2DM severity worsens. Changes in AH composition may serve as an indicator of disease severity, risk assessment of anterior segment cells and structures, and potential future therapies.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0280491
DOI:
10.1371/journal.pone.0280491.g001
DOI:
10.1371/journal.pone.0280491.g002
DOI:
10.1371/journal.pone.0280491.t001
DOI:
10.1371/journal.pone.0280491.t002
DOI:
10.1371/journal.pone.0280491.t003
DOI:
10.1371/journal.pone.0280491.t004
DOI:
10.1371/journal.pone.0280491.t005
DOI:
10.1371/journal.pone.0280491.s001
DOI:
10.1371/journal.pone.0280491.s002
DOI:
10.1371/journal.pone.0280491.s003
DOI:
10.1371/journal.pone.0280491.s004
DOI:
10.1371/journal.pone.0280491.s005
DOI:
10.1371/journal.pone.0280491.s006
DOI:
10.1371/journal.pone.0280491.s007
DOI:
10.1371/journal.pone.0280491.s008
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2267670-3
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