June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Indoleamine 2,3-Dioxygenase (IDO) and Quinolinic Acid (QUIN) Expression in Human Diabetic Retina
Author Affiliations & Notes
  • Ping Hu
    Department of Anatomy, University of Sydney, Camperdown, NSW, Australia
    Ophthalmology, IUPUI, Indianapolis, IN
  • Nicholas Hunt
    Pathology, University of Sydney, Sydney, NSW, Australia
  • Frank Arfuso
    Anatomy, Physiology and Human Biology, University of Western Austrailia, Perth, WA, Australia
  • Lynn Calvin Shaw
    Ophthalmology, IUPUI, Indianapolis, IN
  • Maria B Grant
    Ophthalmology, IUPUI, Indianapolis, IN
    Pharmacology and Therapeutics, University of Florida, Gainesville, FL
  • Tailoi Chan-Ling
    Department of Anatomy, University of Sydney, Camperdown, NSW, Australia
  • Footnotes
    Commercial Relationships Ping Hu, None; Nicholas Hunt, None; Frank Arfuso, None; Lynn Shaw, None; Maria Grant, None; Tailoi Chan-Ling, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4299. doi:
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      Ping Hu, Nicholas Hunt, Frank Arfuso, Lynn Calvin Shaw, Maria B Grant, Tailoi Chan-Ling; Indoleamine 2,3-Dioxygenase (IDO) and Quinolinic Acid (QUIN) Expression in Human Diabetic Retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4299.

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

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Abstract

Purpose: IDO is the first, and rate-limiting, enzyme in the kynurenine pathway (KP). Cytokines produced by activated microglia/macrophages can enhance IDO activity, which can increase the downstream production of QUIN via the KP. QUIN is considered to act as a neurotoxin and pro-inflammatory mediator in some inflammatory and neuronal degenerative diseases, such as Alzheimer’s disease. In this study we investigated the relationship between inflammation and neuronal loss and the expression of IDO and QUIN in human type 1 diabetes (T1D) and type 2 diabetes (T2D).

Methods: Seven T1D, ten T2D and seventeen age-matched non-diabetic human retinas were examined using immunohistochemistry for IDO, QUIN, CD39, ionized calcium-binding adaptor molecule (Iba-1), Neuronal Nuclei (NeuN), and UEA1 lectin.

Results: CD39+/Iba-1+ resident microglia and CD39-/Iba-1+ bone marrow derived macrophages were present at 20% higher density in T1D and T2D retinas than non-diabetic retinas. The density and brightness of IDO+ microglia and the IDO expression on blood vessels were increased significantly in both T1D and T2D retinas. A few QUIN+ microglia-like cells (0.64 ± 0.3/mm2) were seen in 60% of non-diabetic retinas, while the density of QUIN+ microglia-like cells was increased 30- fold in T1D and 10-fold in T2D retinas. Bright QUIN+ Müller cells spanning radially across the entire retina from internal limiting membrane to outer limiting membrane were evident across the entire T1D and T2D retinas. T1D retinas showed a 52% loss of NeuN+ neurons compared to non-diabetic retinas.

Conclusions: Our study suggests that in human diabetic retinas, IDO and QUIN up-regulation could contribute to neuronal degeneration and inflammation. Our results suggest that the KP may play a previously unrecognized role in the pathogenesis of retinopathy associated with both T1D and T2D.

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