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R. A. Gubitosi-Klug, R. Talahalli; Cytosolic Phospholipase A2 Regulates Diabetes-induced Inflammatory Changes in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):30.
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Cytosolic phospholipase A2 (cPLA2) releases arachidonic acid for synthesis of potent inflammatory mediators including the leukotrienes and prostaglandins. We investigated the role of cytosolic phospholipase A2 in regulating the inflammatory response in the diabetic retina.
Retinas from non-diabetic and diabetic wild-type Balbc mice (WT) and non-diabetic and diabetic mice deficient in cPLA2 were analyzed and compared for 1) degeneration of capillaries and loss of pericytes following trypsin digestion and 2) markers of inflammation including tumor necrosis factor alpha (TNFalpha), NF-kappaB, monocyte chemoattractant protein 1 (MCP-1), and intracellular adhesion molecule 1 (ICAM-1) by immunohistochemistry of retinal sections.
Diabetic WT mice had increased capillary degeneration and pericyte loss compared to non-diabetic WT mice, whereas diabetic mice deficient in cPLA2 developed significantly less of both. (p<0.001) Inflammatory responses regulated by cPLA2 activation have been associated with 1) alterations in cytokine and pro-inflammatory gene expression (e.g., TNFalpha and NF-kappaB) and 2) effects on chemotaxis (e.g., expression of MCP-1 and ICAM-1). Immunostaining of paraffin sections of WT retinas indicated a significant diabetes-induced increase in the expression of TNFalpha, NF-kappaB, MCP-1,and ICAM-1. In contrast, retinal sections from mice deficient in cPLA2 lacked these pro-inflammatory changes.
Diabetic mice deficient in cPLA2 developed less histopathologic lesions and expressed less inflammatory markers suggesting involvement of cPLA2 in the development of diabetic retinopathy.
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