ELEVATED MESSENGER-RNA EXPRESSION OF BRAIN-DERIVED NEUROTROPHIC FACTOR IN RETINAL GANGLION-CELL LAYER AFTER OPTIC-NERVE INJURY

Purpose. Recent studies show that exogenous brain-derived neurotrophic factor (BDNF) can promote retinal ganglion cell survival in vivo and in vitro. BDNF is expressed by a subpopulation of cells in the ganglio n cell layer (GCL). To investigate whether endogenous BDNF may play a role in neuronal protection after ganglion cell trauma, BDNF: expressi on in the retina was examined after optic nerve (ON) injury. Methods. The optic nerve in Sprague-Dawley rats was crushed intraorbitally post erior to the optic disc. For controls, the optic nerve on the opposite side in each animal was similarly exposed but was not crushed. After intervals of 6 hours to 6 weeks, eye tissues were processed for in sit u hybridization, Northern blot, and RNase protection assay using radio labeled rat riboprobes. Results. After ON injury, BDNF expression was significantly elevated in cells restricted to the GCL, and more cells demonstrated expression of BDNF than were observed in the controls. El evated BDNF expression was first observed at 24 hours, peaked at 48 ho urs, and declined to the basal level 2 weeks after ON injury. Quantita tive analysis showed a fivefold to sixfold increase in the number of B DNF-positive cells and a 54% increase in BDNF signal intensity in indi vidual cells in the GCL 48 hours after ON injury. In control retinas w ithout ON injury, BDNF expression was localized to some cells in the G CL, as was observed in normal eyes without surgery. Northern blot and RNase protection assay demonstrated a 38% elevation in BDNF expression above control levels 48 hours after ON injury. Conclusions, These res ults indicate that cells in the GCL can upregulate gene expression of BDNF in response to ganglion cell axonal injury and suggest that endog enous BDNF may contribute to a natural neuroprotective process after O N injury.