PMID- 11133879
OWN - NLM
STAT- MEDLINE
DCOM- 20010118
LR  - 20081121
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 42
IP  - 1
DP  - 2001 Jan
TI  - A combination of CNTF and BDNF rescues rd photoreceptors but changes rod 
      differentiation in the presence of RPE in retinal explants.
PG  - 275-82
AB  - PURPOSE: To gather information regarding the combination of ciliary neurotrophic 
      factor (CNTF) and brain-derived neurotrophic factor (BDNF), compared with the 
      individual factors when used as a treatment to retard photoreceptor cell loss in 
      rd mouse retina explants and to investigate the observation that the retinal 
      pigment epithelium (RPE) influences rod differentiation by this treatment. 
      METHODS: Postnatal day (PN)2 or PN7 control and rd mouse retinas were grown with 
      attached retinal pigment epithelium (RPE). The explants were kept in culture up 
      to PN28. During this culture period CNTF, BDNF, CNTF+BDNF, or vehicle were 
      continuously administered to the culture medium. The nontrophic factors 
      cyclosporin A and N:-CBZ-aspartic acid-glutamic acid-valine-aspartic 
      acid-fluoromethyl ketone (z-DEVD-fmk) were also used. The number of photoreceptor 
      nuclei remaining in the outer nuclear layer (ONL) was analyzed in hematoxylin and 
      eosin-stained sections. Rod- and cone-specific antibodies were used to determine 
      identity and state of differentiation of the photoreceptors. RESULTS: Compared 
      with vehicle treatment, BDNF or CNTF resulted in 1.4- or 2-fold more surviving 
      cell rows in the ONL, respectively. However, when CNTF and BDNF were applied 
      together, surviving ONL cell counts in the rd explants were approximately 3 times 
      those in vehicle-treated explants. In the presence of CNTF or CNTF+BDNF, opsin 
      and arrestin expression in rods was decreased compared with rods without attached 
      RPE. Cyclosporin A and z-DEVD-fmk did not show rescue of rd photoreceptor cells. 
      CONCLUSIONS: CNTF or BDNF treatment of rd retinal explants delays photoreceptor 
      cell loss to some extent. However, when these agents are combined, photoreceptor 
      rescue is much more effective. The quenching of opsin and arrestin expression 
      caused by treatment suggests that simultaneous with rod rescue, rod 
      differentiation is depressed. Regarding retinal degeneration, the results from 
      the selective inhibitors of apoptosis rank the CNTF+BDNF combination treatment as 
      the most consistent and effective experimental pharmacologic intervention 
      currently available.
FAU - Caffe, A R
AU  - Caffe AR
AD  - Department of Zoology, Goteborg University, Sweden.
FAU - Soderpalm, A K
AU  - Soderpalm AK
FAU - Holmqvist, I
AU  - Holmqvist I
FAU - van Veen, T
AU  - van Veen T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Arrestin)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Ciliary Neurotrophic Factor)
RN  - 0 (Rod Opsins)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Arrestin/metabolism
MH  - Brain-Derived Neurotrophic Factor/*therapeutic use
MH  - Cell Differentiation/*drug effects
MH  - Cell Survival/drug effects
MH  - Ciliary Neurotrophic Factor/*therapeutic use
MH  - Coculture Techniques
MH  - Drug Therapy, Combination
MH  - Immunoenzyme Techniques
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Organ Culture Techniques
MH  - Photoreceptor Cells, Vertebrate/drug effects
MH  - Pigment Epithelium of Eye/*pathology
MH  - Retinal Degeneration/*drug therapy/metabolism/pathology
MH  - Retinal Rod Photoreceptor Cells/metabolism/*pathology
MH  - Rod Opsins/metabolism
EDAT- 2001/01/03 11:00
MHDA- 2001/02/28 10:01
CRDT- 2001/01/03 11:00
PHST- 2001/01/03 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2001/01/03 11:00 [entrez]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2001 Jan;42(1):275-82.