title: Neurotrophins and neurotrophin receptors in proliferative diabetic retinopathy.
abstract: Neurotrophins (NTs) are emerging as important mediators of angiogenesis and fibrosis. We investigated the expression of the NTs nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) and their receptors TrkA, TrkB, and TrkC in proliferative diabetic retinopathy (PDR). As a comparison, we examined the expression of NTs and their receptors in the retinas of diabetic rats. Vitreous samples from 16 PDR and 15 nondiabetic patients were studied by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). Epiretinal membranes from 17 patients with PDR were studied by immunohistochemistry. Rats were made diabetic with a single high dose of streptozotocin and retinas of rats were examined by Western blot analysis. Western blot analysis revealed a significant increase in the expression of NT-3 and NT-4 and the shedding of receptors TrkA and TrkB in vitreous samples from PDR patients compared to nondiabetic controls, whereas NGF and BDNF and the receptor TrkC were not detected with the use of Western blot analysis and ELISA. In epiretinal membranes, vascular endothelial cells and myofibroblasts expressed NT-3 and the receptors TrkA, TrkB and TrkC in situ, whereas NT-4 was not detected. The expression levels of NT-3 and NT-4 and the receptors TrkA and TrkB, both in intact and solubilized forms, were upregulated in the retinas of diabetic rats, whereas the receptor TrkC was not detected. Co-immunoprecipitation studies revealed binding between NT-3 and the receptors TrkA and TrkB in the retinas of diabetic rats. Our findings in diabetic eyes from humans and rats suggest that the increased expression levels within the NT-3 and NT-4/Trk axis are associated with the progression of PDR.
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. abuasrar@KSU.edu.sa
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Abu El-Asrar
authors.forename: Ghulam
authors.initials: G
authors.lastname: Mohammad
authors.forename: Gert
authors.initials: G
authors.lastname: De Hertogh
authors.forename: Mohd Imtiaz
authors.initials: MI
authors.lastname: Nawaz
authors.forename: Kathleen
authors.initials: K
authors.lastname: Van Den Eynde
authors.forename: Mohammad Mairaj
authors.initials: MM
authors.lastname: Siddiquei
authors.forename: Sofie
authors.initials: S
authors.lastname: Struyf
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
authors.forename: Karel
authors.initials: K
authors.lastname: Geboes
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology*; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology; D014822:Vitreous Body / Q000378:metabolism / Q000473:pathology
chemical_list: D043925:Angiogenesis Inducing Agents; D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor