EFFECTS OF OCULAR INJURY AND ADMINISTRATION OF BRAIN-DERIVED NEUROTROPHIC FACTOR ON SURVIVAL AND REGROWTH OF AXOTOMIZED RETINAL GANGLION-CELLS

Optic nerve transection in adult rats results in the death of approxim ate to 50% of the axotomized retinal ganglion cells (RGCs) by 1 week a nd nearly 90% by 2 weeks after injury. The capacity of brain-derived n eurotrophic factor (BDNF) to prevent this early, severe loss of RGCs w as investigated in vivo by intravitreal injections of BDNF [5 mu g in 5 mu l of bovine serum albumin/phosphate-buffered saline (BSA/PBS)] or vehicle (5 mu l of BSA/PBS). Using quantitative anatomical techniques , we show that (i) all RGCs survived 1 week after a single injection o f BDNF at the time of axotomy. (ii) RGC densities decreased in the BDN F-treated retinas by 2 weeks but remained significantly greater than i n the untreated controls. (iii) An enhanced RGC survival was obtained with single injections of BDNF from 6 days before to 5 days after axot omy. (iv) Repeated injections resulted in greater numbers of surviving RGCs, an effect that declined to undetectable levels by 6 weeks. (v) There were indications for an endogenous local source of trophic suppo rt whose expression was triggered by ocular injury, particularly to th e anterior part of the eye. (vi) With multiple BDNF injections, there was profuse axonal sprouting around the optic disc. This remarkable in traretinal growth was not, however, reflected in increased RGC innerva tion of the peripheral nerve grafts, which are known to facilitate reg eneration when used as optic nerve substitutes.