PMID- 18326759 OWN - NLM STAT- MEDLINE DCOM- 20080415 LR - 20091119 IS - 0146-0404 (Print) IS - 0146-0404 (Linking) VI - 49 IP - 3 DP - 2008 Mar TI - BDNF increases survival of retinal dopaminergic neurons after prenatal compromise. PG - 1282-9 LID - 10.1167/iovs.07-0521 [doi] AB - PURPOSE: Chronic placental insufficiency (CPI) severe enough to cause growth restriction (GR) results in alterations to the retina, including a reduction in tyrosine hydroxylase immunoreactive (TH-IR)-dopaminergic amacrine cells. Brain-derived neurotrophic factor (BDNF) plays a role in the development of the retinal dopaminergic network and may therefore be an appropriate therapy for restoring dopaminergic cells after prenatal compromise. This study was conducted (1) to establish whether BDNF and its receptor NTRK2 (Trk B) are altered in the retina after CPI and (2) to explore the potential of BDNF to enhance dopaminergic cell survival in organotypic retinal cultures from prenatally compromised animals. METHODS: CPI was induced in pregnant guinea pigs at 30 days' gestation (dg; term, approximately 67 dg) via unilateral ligation of the uterine artery. Fetuses were euthanatized at 60 dg and the retinas prepared for enzyme-linked immunosorbent assay (ELISA) analysis of BDNF protein levels and for immunohistochemistry to localize BDNF and NTRK2. Organotypic cultures of retinas from GR and control fetuses at 50 to 52 dg were treated with BDNF, and dopaminergic amacrine cells counts were assessed. RESULTS: Retinal BDNF protein levels and the intensity of BDNF-immunoreactivity (IR) in the ganglion cell layer were reduced (P < 0.05) in GR fetuses compared with control fetuses. Addition of BDNF to organotypic cultures increased (P < 0.05) the survival and neurite growth of dopaminergic neurons from both control and GR fetuses. CONCLUSIONS: Alterations to BDNF levels may underlie reductions in dopaminergic amacrine cells observed after CPI. The addition of BDNF has the potential to increase survival and neurite growth of dopaminergic amacrine cells. FAU - Loeliger, Michelle M AU - Loeliger MM AD - Department of Anatomy and Cell Biology, University of Melbourne, Melbourne, Victoria, Australia. m.loeliger@unimelb.edu.au FAU - Briscoe, Todd AU - Briscoe T FAU - Rees, Sandra M AU - Rees SM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Invest Ophthalmol Vis Sci JT - Investigative ophthalmology & visual science JID - 7703701 RN - 0 (Brain-Derived Neurotrophic Factor) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Amacrine Cells/cytology/*metabolism MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology MH - Cell Count MH - Cell Survival/drug effects/physiology MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Fetal Growth Retardation/*metabolism MH - Guinea Pigs MH - Immunoenzyme Techniques MH - Organ Culture Techniques MH - Placental Insufficiency/*metabolism MH - Pregnancy MH - Receptor, trkB/*metabolism MH - Retina/drug effects/*metabolism MH - Retinal Ganglion Cells/metabolism MH - Tyrosine 3-Monooxygenase/*metabolism EDAT- 2008/03/11 09:00 MHDA- 2008/04/16 09:00 CRDT- 2008/03/11 09:00 PHST- 2008/03/11 09:00 [pubmed] PHST- 2008/04/16 09:00 [medline] PHST- 2008/03/11 09:00 [entrez] AID - 49/3/1282 [pii] AID - 10.1167/iovs.07-0521 [doi] PST - ppublish SO - Invest Ophthalmol Vis Sci. 2008 Mar;49(3):1282-9. doi: 10.1167/iovs.07-0521.