Elevated Expression of AOC3 in Human Eyes with NPDR

Abstract

Purpose : A number of studies have indicated that inflammatory processes contribute to the development diabetic retinopathy (DR). Moreover, in animal models anti-inflammatory therapies appear to significantly inhibit the development of DR. AOC3 (Amine oxidase, copper containing 3), also known as VAP-1, can act to recruit inflammatory cells from the microvasculature and facilitates extravasation of neutrophils. Here we describe the distribution of AOC3 in different parts of the retina of human diabetes mellitus (DM) donors with and without DR and determine its relationship with underlying structural changes associated with non-proliferative diabetic retinopathy (NPDR).

Methods : Sagittal retinal sections were prepared from human donor eyes with a clinically documented diagnosis of non-proliferative DR. These included samples with microaneurysms (n=5), hemorrhages (n=5), IntraRetinal Microvascular Abnormalities (IRMA) (n=5), venous beadings (n=3), macula edema (n=5) and hard exudates (n=5). Controls included individuals with DM but without signs of DR (N=9) as well as age-matched controls without DM or DR (n=5). Accumulation of AOC3 was visualized by immunohistochemistry and labeling intensities associated with the retinal vasculature, retinal parenchyma, or choroidal vasculature were independently graded on a 5-point scale by two investigators blinded to the disease status. The resulting ordinal data was analyzed using Kruskall-Wallis test (ANOVA) followed by Dunn's test in order to compare individual DR subtypes as well as the combined NPDR group with the controls.

Results : A low level of diffuse AOC3 expression in the parenchyma of the inner retina is detected in the vast majority of all samples but levels do not appear to be correlated with the presence of NPDR. AOC3 labeling associated with the choroidal vasculature is marginally higher in eyes with NPDR than in either group of controls, but statistical significance is not reached. In contrast, the retinal vasculature displays a marked increase in AOC3 labeling in all samples with DR, regardless of subtype. These data are highly significant with respect to either the age-matched healthy controls (p=0.026) or the DM control group (p=0.0002).

Conclusions : AOC3 expression is elevated in the retinal, but not choroidal, vasculature in human eyes with NPDR. The findings suggest that blocking AOC3 mediated leukocyte recruitment could be a viable approach to reduce retinal inflammation in DR patients.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.