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M. Eladl, R. Mussell, K. Kahook, A. Tawfik, K. Maddipati, J. J. Nussbaum, M. A. Al-Shabrawey, II; Increased Production of Hydroxyeicosatetraneoic Acids in Proliferative Diabetic Retinopathy and Oxygen-Induced Retinopathy: Implication In Retinal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5623.
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Angiogenesis is the formation of new blood vessels from preexisting ones. It is crucial for the development and progression of ischemic retinopathy, which develops in various retinal disorders, including diabetic retinopathy (DR), retinopathy of prematurity (ROP) and retinal vein occlusion. Ischemic retinopathy remains a common cause of visual impairment and blindness in the world due to relatively ineffective treatment. The hallmark of ischemic retinopathy is the retinal neovascularization. Arachidonic acid (AA) metabolites, which are collectively known as eicosanoids, are also involved in regulating angiogenesis. Angiogenesis has been shown to be promoted by the metabolic products of cycloxygenase (COX2), prostaglandins and the products of lipoxygenase (LOX) system, which include leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs). The purpose of this study was to elucidate if there is a link between lipoxygenase pathway of AA metabolism and retinal neovascularization.
Vitreous samples obtained from patients undergoing vitrectomy because of proliferative diabetic retinopathy (PDR) or other causes as control. Retinas were collected from mice with oxygen-induced retinopathy (OIR) and age matched normal mice. Vitreous samples and retinal homogenates were analyzed for the amount of 5, 12 and 15-HETEs using LC/MS. Retinal homogenates were also analyzed for the expression of 12-lipoxygenase using Western blotting.
LC/MS analysis of HETEs production in vitreous samples and retinal homogenates showed significant Increases in the amount of 5, 15 and 12-HETEs in subjects with PDR and in mice with OIR compared with their controls. Retinal neovascularization was also associated with increased expression of both leukocyte and platelet 12-lipoxygenase.
HETEs are involved in retinal neovascularization, thus targeting lipoxygenase pathway of AA metabolism could be a novel therapeutic intervention to treat ischemic retinopathy.
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