EFFECTS OF GDNF ON RETINAL GANGLION-CELL SURVIVAL FOLLOWING AXOTOMY

Recent evidence suggests that approximate to 90% of retinal ganglion c ells (RGCs) die by the process of apoptosis within 14 days of optic ne rve transection. RGCs begin to disappear from the retina between 5 and 7 days postaxotomy when the highest percentage of RGCs show character istics typical of apoptosis. A single intraocular injection of glial c ell-line derived neurotrophic factor (GDNF) given at the time of axoto my resulted in a delay in the initiation of RGC death and increased th e densities of surviving RGCs at 7, 10 and 14 days postaxotomy. The me an RGC densities in GDNF treated retinas at 7 (2381 +/- 144), 10 (1561 +/- 117) and 14 (1123 +/- 116) days postaxotomy were significantly hi gher than that of controls (1835 +/- 82, 835 +/- 272 and 485 +/- 39, r espectively). The loss of RGCs was paralleled by increases in TUNEL po sitive staining in control retinas and a lower percentage of TUNEL pos itive cells in GDNF treated retinas at 5, 7 and 10 days postaxotomy. T hese results suggest that GDNF is capable of promoting RGC survival fo llowing injury, possibly by interfering with an essential step in apop tosis. (C) 1998 Elsevier Science Ltd. All rights reserved.