Expression of lysophosphatidic acid, autotaxin and acylglycerol kinase

• Published in: Acta ophthalmologica (Oxford, England) Vol. 90; no. s249
• Main Authors: ABU EL ASRAR, A, MOHAMMAD, G, NAWAZ, MI, SIDDIQUEI, M, KANGAVE, D, OPDENAKKER, G
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2012; Wiley Subscription Services, Inc
• Subjects: Diabetes; Diabetic retinopathy; Ophthalmology; Rodents; Vascular endothelial growth factor
• ISSN: 1755-375X; 1755-3768
• DOI: 10.1111/j.1755-3768.2012.2683.x

Purpose To measure the levels of LPA and LPA‐producing enzymes, autotaxin (ATX) and acylglycerol kinase (AGK) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate their levels with clinical disease activity and the level of vascular endothelial growth factor (VEGF). In addition, we examined the expression of ATX, AGK and VEGFR‐2 in the retinas of diabetic rats. Methods Vitreous samples from 42 PDR and 35 nondiabetic patients were studied by enzyme‐linked immunosorbent assay. Vitreous samples and retinas of rats were examined by Western blot analysis. Results VEGF, LPA and AGK levels in vitreous samples from PDR patients were significantly higher than those in control patients without diabetes (p<0.001 for all comparisons). ATX levels in PDR with active neovascularization and inactive PDR were significantly lower than those in nondiabetic patients (p=0.045). Mean VEGF and AGK levels in PDR with active neovascularization were significantly higher than those in inactive PDR and nondiabetic patients (p<0.001 for both comparisons). A significant correlation was observed between levels of VEGF and levels of AGK in PDR patients (r=0.954, p<0.001). Western blot analysis revealed a significant increase in the expression of AGK and VEGFR‐2 in vitreous samples and the retinas of diabetic rats compared to nondiabetic controls, whereas ATX was significantly downregulated. Conclusion ATX‐AGK‐LPA signaling axis might be an important player in the development and progression of diabetic retinopathy.