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 approximately 50% of the axotomized retinal ganglion cells (RGCs) by 1 week and nearly 90% by 2 weeks after injury. The capacity of brain-derived neurotrophic factor (BDNF) to prevent this early, severe loss of RGCs was investigated in vivo by intravitreal injections of BDNF [5 micrograms in 5 microliters of bovine serum albumin/phosphate-buffered saline (BSA/PBS)] or vehicle (5 microliters of BSA/PBS). Using quantitative anatomical techniques, we show that (i) all RGCs survived 1 week after a single injection of BDNF at the time of axotomy. (ii) RGC densities decreased in the BDNF-treated retinas by 2 weeks but remained significantly greater than in the untreated controls. (iii) An enhanced RGC survival was obtained with single injections of BDNF from 6 days before to 5 days after axotomy. (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 support whose expression was triggered by ocular injury, particularly to the anterior part of the eye. (vi) With multiple BDNF injections, there was profuse axonal sprouting around the optic disc. This remarkable intraretinal growth was not, however, reflected in increased RGC innervation of the peripheral nerve grafts, which are known to facilitate regeneration when used as optic nerve substitutes.
Mansour-Robaey
S
S
Centre for Research in Neuroscience, Montreal General Hospital Research Institute, PQ, Canada.
Clarke
D B
DB
Wang
Y C
YC
Bray
G M
GM
Aguayo
A J
AJ
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor; D002470:Cell Survival / Q000187:drug effects; D005131:Eye Injuries / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D005260:Female; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009900:Optic Nerve / Q000187:drug effects / Q000502:physiology; D020221:Optic Nerve Injuries; D010525:Peripheral Nerves / Q000187:drug effects / Q000502:physiology / Q000637:transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins