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. 2020 Oct 9;21(20):7451.
doi: 10.3390/ijms21207451.

Eicosanoid Profiles in the Vitreous Humor of Patients with Proliferative Diabetic Retinopathy

Albert L Lin  1 , Richard J Roman  2 , Kathleen A Regan  3 , Charlotte A Bolch  4 , Ching-Jygh Chen  1 , Siva S R Iyer  4
Affiliations

Eicosanoid Profiles in the Vitreous Humor of Patients with Proliferative Diabetic Retinopathy

Albert L Lin et al. Int J Mol Sci. .

Abstract

Proliferative diabetic retinopathy is a potentially blinding sequela of uncontrolled diabetes that involves a complex interaction of pro-angiogenic and inflammatory pathways. In this study, we compared the levels of pro-angiogenic arachidonic acid-derived mediators in human vitreous humor obtained from eyes with high-risk proliferative diabetic retinopathy versus controls. The results indicated that lipoxygenase and cytochrome P450-derived eicosanoids were elevated (5-HETE, 12-HETE, 20-HETE, and 20-COOH-AA), and there appeared to be no differences in levels measured in eyes with tractional retinal detachments versus those without. These results provide further insight into the pathogenesis of this disease and for the development of future potential therapeutic agents that target arachidonic acid metabolites to treat diabetic retinopathy.

Keywords: eicosanoids; proliferative diabetic retinopathy; tractional retinal detachment; vitreous.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
A schematic of arachidonic acid’s hydroxyeicosatetraenoic (HETE), and epoxyeicosatrienoic acid (EET) derivatives and their relationships. HETEs are created by both the lipoxygenase (5-HETE, 12-HETE, 15-HETE) and cytochrome P450 (16-HETE, 18-HETE, 19-HETE, 20-HETE) pathways with dihydroxyeicosatraenoic acid (DiHETE) derived from EET by soluble expoxide hydrolase. 20-carboxy-arachidonic acid (20-COOH-AA) is a metabolite of 20-HETE. Eicosanoids that were significantly different in the vitreous of control and PDR eyes in the current study are shown in bold font COX = cyclooxygenase. HETEs and their derivatives have a role in pro-angiogenic processes [17,18,19,20,21,22,23,24,25,26,27,28].
Figure 2
Figure 2
Human vitreous levels of eicosanoids in PDR (n = 31) vs. control (n = 13) eyes. Comparison of levels (pg/mL) of 5-HETE, 12-HETE, 15-HETE, 12-HETrE, and 19-HETE in PDR vs. controls. * denotes statistical significance (p < 0.05).
Figure 3
Figure 3
Human vitreous levels of eicosanoids in PDR (n = 31) vs. control (n = 13) eyes. Comparison of levels (pg/mL) of individual EET and DiHETE, as well as total levels in PDR vs. controls. * denotes statistical significance (p < 0.05).
Figure 4
Figure 4
Human vitreous levels of eicosanoids in PDR (n = 31) vs. control (n = 13) eyes. Comparison of levels (pg/mL) of 20-HETE, 20-COOH-AA in PDR vs. controls. * denotes statistical significance (p < 0.05).
Figure 5
Figure 5
Human vitreous levels of eicosanoids in PDR subtypes treated with bevacizumab, VH (n = 11) vs. TRD (n = 8) eyes. Comparison of levels (pg/mL) of 5-HETE, 12-HETE, 15-HETE, 12-HETrE, and 19-HETE in VH vs. TRD.
Figure 6
Figure 6
Human vitreous levels of eicosanoids in PDR subtypes treated with bevacizumab, VH (n = 11) vs. TRD (n = 8) eyes. Comparison of levels (pg/mL) of individual EET and DiHETE as well as total levels in VH vs. TRD.
Figure 7
Figure 7
Human vitreous levels of eicosanoids in PDR subtypes treated with bevacizumab, VH (n = 11) vs. TRD (n = 8) eyes. Comparison of levels (pg/mL) of 20-HETE, 20-COOH-AA in VH vs. TRD.
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