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Published on: September 17, 2014
BDNF increases survival of retinal dopaminergic neurons after prenatal compromise
Michelle M Loeliger1, Todd Briscoe, Sandra M Rees
1Department of Anatomy and Cell Biology, University of Melbourne, Melbourne, Victoria, Australia. m.loeliger@unimelb.edu.au
Insights
Chronic placental insufficiency (CPI) reduces retinal brain-derived neurotrophic factor (BDNF), impacting dopaminergic cells. Supplementing with BDNF promotes survival and growth of these crucial retinal neurons.
Area of Science:
- Neuroscience
- Developmental Biology
- Ophthalmology
Background:
- Chronic placental insufficiency (CPI) causes fetal growth restriction (GR), leading to retinal alterations, specifically a loss of dopaminergic amacrine cells.
- Brain-derived neurotrophic factor (BDNF) is vital for retinal dopaminergic network development and may offer therapeutic potential for prenatal insults.
Purpose of the Study:
- To investigate alterations in retinal BDNF and its receptor NTRK2 (Trk B) in fetuses with CPI-induced GR.
- To explore the efficacy of BDNF in enhancing dopaminergic cell survival in ex vivo retinal cultures from prenatally compromised fetuses.
Main Methods:
- CPI was induced in guinea pigs via uterine artery ligation.
- Retinal BDNF and NTRK2 levels were analyzed using ELISA and immunohistochemistry.
- Organotypic retinal cultures from GR and control fetuses were treated with BDNF to assess dopaminergic amacrine cell survival.
Main Results:
- GR fetuses exhibited reduced retinal BDNF protein levels and decreased BDNF-immunoreactivity (IR) in the ganglion cell layer.
- BDNF treatment significantly increased dopaminergic neuron survival and neurite growth in retinal cultures from both control and GR fetuses.
Conclusions:
- Reduced BDNF levels in the retina may contribute to the loss of dopaminergic amacrine cells following CPI.
- Exogenous BDNF demonstrates potential as a therapeutic agent to promote dopaminergic cell survival and neurite outgrowth in the context of prenatal compromise.
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.
