PMID- 10686086 OWN - NLM STAT- MEDLINE DCOM- 20000329 LR - 20081121 IS - 0014-4886 (Print) IS - 0014-4886 (Linking) VI - 161 IP - 2 DP - 2000 Feb TI - Growth factors in combination, but not individually, rescue rd mouse photoreceptors in organ culture. PG - 676-85 AB - The rd mouse retina is an animal model for human retinal dystrophy in which the rod photoreceptors undergo apoptosis during the first 4 weeks in vivo or in organ culture. We have examined the effect of different families of trophic factors on the survival of rd mouse photoreceptors in organ culture. Retinas were harvested from rd mice at postnatal day 2 and grown in organ culture for 27 days in vitro (DIV) in DMEM with 10% fetal calf serum. Ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF), fibroblast growth factor-2 (FGF2), glial cell line-derived neurotrophic factor (GDNF), neurturin, and persephon were added individually or in combination to the medium at a dose of 50 ng/ml or less. CNTF + BDNF in combination resulted in photoreceptor survival comparable to wild-type retinas after 27 DIV. CNTF + FGF2 or CNTF + GDNF produced a partial prevention of photoreceptor death. Photoreceptor degeneration was not blocked by any of the trophic factors added individually. A significant increase in photoreceptor survival was seen with forskolin added to CNTF, but not to BDNF, FGF2, or GDNF. These results demonstrate that trophic factors promote photoreceptor survival through a synergistic interaction. Increased understanding of receptor interactions and signaling pathways may lead to a potential therapeutic role for combinatorial trophic factors in treatment of photoreceptor dystrophies. CI - Copyright 2000 Academic Press. FAU - Ogilvie, J M AU - Ogilvie JM AD - Fay and Carl Simons Center for Biology of Hearing and Deafness, Central Institute for the Deaf, St. Louis, Missouri, 63110, USA. FAU - Speck, J D AU - Speck JD FAU - Lett, J M AU - Lett JM LA - eng GR - K17 NS0156/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Ciliary Neurotrophic Factor) RN - 0 (GDNF protein, human) RN - 0 (Gdnf protein, mouse) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Growth Substances) RN - 0 (NRTN protein, human) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neurturin) RN - 0 (Nrtn protein, mouse) RN - 103107-01-3 (Fibroblast Growth Factor 2) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/pharmacology MH - Cell Survival/drug effects MH - Ciliary Neurotrophic Factor/pharmacology MH - Disease Models, Animal MH - Drug Interactions MH - Fibroblast Growth Factor 2/pharmacology MH - Glial Cell Line-Derived Neurotrophic Factor MH - Growth Substances/*pharmacology MH - Homozygote MH - Humans MH - Mice MH - Mice, Inbred C57BL MH - Mice, Mutant Strains MH - Nerve Growth Factors/*pharmacology MH - Nerve Tissue Proteins/pharmacology MH - Neurturin MH - Organ Culture Techniques MH - Photoreceptor Cells, Vertebrate/cytology/drug effects/*pathology MH - Retina/pathology MH - Retinal Degeneration/genetics/*pathology MH - Time Factors EDAT- 2000/02/25 09:00 MHDA- 2000/04/01 09:00 CRDT- 2000/02/25 09:00 PHST- 2000/02/25 09:00 [pubmed] PHST- 2000/04/01 09:00 [medline] PHST- 2000/02/25 09:00 [entrez] AID - S0014-4886(99)97291-6 [pii] AID - 10.1006/exnr.1999.7291 [doi] PST - ppublish SO - Exp Neurol. 2000 Feb;161(2):676-85. doi: 10.1006/exnr.1999.7291.