PMID- 23762379 OWN - NLM STAT- MEDLINE DCOM- 20140122 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 6 DP - 2013 TI - Neurotrophins and neurotrophin receptors in proliferative diabetic retinopathy. PG - e65472 LID - 10.1371/journal.pone.0065472 [doi] LID - e65472 AB - 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. FAU - Abu El-Asrar, Ahmed M AU - Abu El-Asrar AM AD - Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. abuasrar@KSU.edu.sa FAU - Mohammad, Ghulam AU - Mohammad G FAU - De Hertogh, Gert AU - De Hertogh G FAU - Nawaz, Mohd Imtiaz AU - Nawaz MI FAU - Van Den Eynde, Kathleen AU - Van Den Eynde K FAU - Siddiquei, Mohammad Mairaj AU - Siddiquei MM FAU - Struyf, Sofie AU - Struyf S FAU - Opdenakker, Ghislain AU - Opdenakker G FAU - Geboes, Karel AU - Geboes K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130607 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Angiogenesis Inducing Agents) RN - 0 (Nerve Growth Factors) RN - 0 (Receptors, Nerve Growth Factor) SB - IM MH - Angiogenesis Inducing Agents/metabolism MH - Animals MH - Blotting, Western MH - Diabetic Retinopathy/*metabolism/*pathology MH - Endothelial Cells/metabolism/pathology MH - Humans MH - Immunohistochemistry MH - Immunoprecipitation MH - Male MH - Nerve Growth Factors/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Nerve Growth Factor/*metabolism MH - Retinal Vessels/metabolism/pathology MH - Vitreous Body/metabolism/pathology PMC - PMC3676317 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2013/06/14 06:00 MHDA- 2014/01/23 06:00 PMCR- 2013/06/07 CRDT- 2013/06/14 06:00 PHST- 2012/10/23 00:00 [received] PHST- 2013/04/25 00:00 [accepted] PHST- 2013/06/14 06:00 [entrez] PHST- 2013/06/14 06:00 [pubmed] PHST- 2014/01/23 06:00 [medline] PHST- 2013/06/07 00:00 [pmc-release] AID - PONE-D-12-32705 [pii] AID - 10.1371/journal.pone.0065472 [doi] PST - epublish SO - PLoS One. 2013 Jun 7;8(6):e65472. doi: 10.1371/journal.pone.0065472. Print 2013.