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.