June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Profile of vascular permeability factors in aqueous humor of diabetic macular edema
Author Affiliations & Notes
  • Matthew Mason
    Allergan, an AbbVie company, California, United States
  • Kameran Lashkari
    Advanced Eye Centers Inc, North Dartmouth, Massachusetts, United States
  • Sveti Ugarte
    Allergan, an AbbVie company, California, United States
  • Lori-Ann Christie
    Allergan, an AbbVie company, California, United States
  • Gerry Rodrigues
    Allergan, an AbbVie company, California, United States
  • Francisco J Lopez
    Allergan, an AbbVie company, California, United States
  • Footnotes
    Commercial Relationships   Matthew Mason, AbbVie Inc. (E); Kameran Lashkari, None; Sveti Ugarte, AbbVie Inc. (E); Lori-Ann Christie, AbbVie Inc. (E); Gerry Rodrigues, AbbVie Inc. (E); Francisco Lopez, AbbVie Inc. (E)
  • Footnotes
    Support  This study was sponsored by Allergan (prior to its aquisition by AbbVie)
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1068. doi:
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    • Get Citation

      Matthew Mason, Kameran Lashkari, Sveti Ugarte, Lori-Ann Christie, Gerry Rodrigues, Francisco J Lopez; Profile of vascular permeability factors in aqueous humor of diabetic macular edema. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1068.

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

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Abstract

Purpose : Many growth factors and cytokines are involved in the onset of diabetic retinopathy (DR), some promoting increased vascular permeability and neovascularization and contributing to disease progression. Previous investigations into the proteomic signature of Diabetic Macular Edema (DME) have characterized a number of factors; however, many consist of circulating cytokines and chemokines. We hypothesized a model of DME progression, vascular breakdown and edema could be strengthened by comparing known and putative permeability associated markers in the aqueous of diabetic subjects with or without a diagnosis of DME.

Methods : Aqueous humor samples (AH) were collected from 3 sources: Healthy non-diabetic control subjects at cataract surgery (CTL), non-proliferative diabetic retinopathy with absence of DME (NPDR), and NPDR with DME (DME). Samples were collected at Advanced Eye Centers, Dartmouth, MA, and delivered to Allergan/AbbVie, Irvine, CA for analysis. Three multiplex panels (Luminex) spanning 47 soluble protein markers were used to detect protein levels in 108 subject samples (CTL: 42, NPDR: 35, DME: 31).

Results : Of the 47 markers surveyed in DME subject samples, 13 were significantly upregulated when compared to control or NPDR following age-corrected univariate ANCOVA with Dunnett’s correction for multiple comparisons. Upregulated factors included angiopoietin 2, angiostatin, endothelin 1, hepatocyte growth factor, placental growth factor 1, stem cell factor, soluble epidermal growth factor receptor, soluble hepatocyte growth factor receptor, soluble urokinase plasminogen activator surface receptor, and thrombospondin 2 (p values < 0.001). Platelet-derived growth factor B dimer (PDGF AB/BB) was downregulated compared to CTL (p< 0.01).

Conclusions : The strength and potential predictive value of the prospective markers modeled here are demonstrated by principal components analysis (PCA), showing that >70% of variance could be preserved by only two components. These markers were strongly associated with DME when grouped by PCA and >87% of DME subjects could be sorted by a single component (+PC1). Further, >90% of CTL subjects were sorted by PC2 and showed strong positive correlation with expression of a single marker (PDGF AA/BB; 0.624). In summary, these data provide a focused examination of permeability factors in addition to VEGF and present a robust model of AH disease markers highly associated with DME.

This is a 2021 ARVO Annual Meeting abstract.

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