PMID- 10022580 OWN - NLM STAT- MEDLINE DCOM- 19990507 LR - 20191102 IS - 0022-3034 (Print) IS - 0022-3034 (Linking) VI - 38 IP - 3 DP - 1999 Feb 15 TI - Glial cell line-derived neurotrophic factor (GDNF) promotes the survival of axotomized retinal ganglion cells in adult rats: comparison to and combination with brain-derived neurotrophic factor (BDNF). PG - 382-90 AB - Adult rat retinal ganglion cells (RGC) undergo degeneration after optic nerve transection. Studies have shown that exogenously applied neurotrophic factors such as brain-derived neurotrophic factor (BDNF) can attenuate axotomy-induced as well as developmental RGC death. Here, we examined whether glial cell line-derived neurotrophic factor (GDNF), a known neurotrophic factor for dopaminergic neurons and motor neurons, could provide neurotrophic support to RGC in adult rats. We determined whether RGC could retrogradely transport GDNF from their target tissue. After injection into the superior colliculus of adult rats, 125I-GDNF was retrogradely transported to contralateral eyes but not to ipsilateral eyes. The transport of 125I-GDNF could be blocked by coinjection of excess unlabeled GDNF, indicating that it was receptor mediated. We tested whether intravitreally applied GDNF could prevent axotomy-induced RGC degeneration. The RGC were prelabeled with Fluorogold (FG) and axotomized by intraorbital optic nerve transection. GDNF, BDNF (positive control), cytochrome c (negative control), or a GDNF/BDNF combination was injected intravitreally on days 0 and 7. On day 14, FG-labeled RGC were counted from whole-mount retinas. We found that, similar to BDNF, GDNF could significantly attenuate the degeneration of RGC in a dose-dependent fashion. Furthermore, the combination treatment of GDNF and BDNF showed better protection than either factor used individually. Our data indicate that GDNF is a neurotrophic factor for the adult rat RGC. GDNF, like BDNF, may be useful for the treatment of human RGC degenerative diseases. FAU - Yan, Q AU - Yan Q AD - Department of Neuroscience, Amgen, Inc., Thousand Oaks, California 91320, USA. FAU - Wang, J AU - Wang J FAU - Matheson, C R AU - Matheson CR FAU - Urich, J L AU - Urich JL LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - J Neurobiol JT - Journal of neurobiology JID - 0213640 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (GDNF protein, human) RN - 0 (Gdnf protein, rat) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neuroprotective Agents) RN - 0 (Recombinant Proteins) SB - IM MH - Animals MH - Autoradiography MH - *Axotomy MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cell Survival/drug effects MH - Female MH - Glial Cell Line-Derived Neurotrophic Factor MH - Humans MH - *Nerve Growth Factors MH - Nerve Tissue Proteins/*pharmacology MH - Neuroprotective Agents/*pharmacology MH - Optic Nerve/physiology MH - Rats MH - Recombinant Proteins/pharmacology MH - Retinal Ganglion Cells/drug effects/*physiology MH - Superior Colliculi/cytology/physiology MH - Vitreous Body/physiology EDAT- 1999/02/18 03:02 MHDA- 2000/06/20 09:00 CRDT- 1999/02/18 03:02 PHST- 1999/02/18 03:02 [pubmed] PHST- 2000/06/20 09:00 [medline] PHST- 1999/02/18 03:02 [entrez] AID - 10.1002/(SICI)1097-4695(19990215)38:3<382::AID-NEU7>3.0.CO;2-5 [pii] AID - 10.1002/(sici)1097-4695(19990215)38:3<382::aid-neu7>3.0.co;2-5 [doi] PST - ppublish SO - J Neurobiol. 1999 Feb 15;38(3):382-90. doi: 10.1002/(sici)1097-4695(19990215)38:3<382::aid-neu7>3.0.co;2-5.