PMID- 10235570
OWN - NLM
STAT- MEDLINE
DCOM- 19990524
LR  - 20181224
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 40
IP  - 6
DP  - 1999 May
TI  - Repeated injections of a ciliary neurotrophic factor analogue leading to 
      long-term photoreceptor survival in hereditary retinal degeneration.
PG  - 1298-305
AB  - PURPOSE: To determine whether ciliary neurotrophic factor (CNTF) or brain-derived 
      neurotrophic factor (BDNF) treatment leads to long-term photoreceptor survival in 
      hereditary retinal degeneration. METHODS: An autosomal dominant feline model of 
      rod-cone dystrophy was used throughout the study with two normal animals. In the 
      first experiment, intravitreal injections of a human CNTF analogue (Axokine; 
      Regeneron Pharmaceuticals, Tarrytown, NY) were administered to one eye of each 
      animal (n = 10) beginning on postnatal day 10 and were repeated every 4 weeks. 
      Clinical and histopathologic examinations were performed at 5.5, 9.5, and 13.5 
      weeks. In the second experiment, animals (n = 17) were randomly assigned to 
      receive intravitreal injections of either Axokine (at half the initial dose), 
      human BDNF, or the vehicle for Axokine to one eye at 5.5 weeks. The same therapy 
      was repeated every 4 weeks in each group. Clinical and histopathologic 
      examinations were performed at 9.5, 13.5, and 17.5 weeks. Photoreceptor survival 
      was assessed by cell counting. Apoptotic cells were identified by morphology and 
      a modified TdT-dUTP terminal nick-end labeling (TUNEL) technique. In the third 
      experiment, two normal animals were treated with Axokine as in the first 
      experiment. Glial fibrillary acidic protein ((GFAP) immunohistochemistry was 
      performed to assess glial cell reaction. RESULTS: In the first two experiments, 
      Axokine significantly prolonged photoreceptor survival (P < 0.01) and reduced the 
      presence of apoptotic cells (P < 0.05) and TUNEL-positive cells (P < 0.05). In 
      the second experiment, results in the the BDNF- and sham-injected eyes were not 
      significantly different from those in the untreated eyes. Minimal posterior 
      subcapsular cataract and mild retinal folds were found in all Axokine-treated 
      eyes in both dystrophic and normal animals. These complications were milder in 
      the second experiment when injections were started later and at a reduced dose. 
      GFAP immunolabeling was also increased in all Axokine-treated eyes. CONCLUSIONS: 
      Axokine, but not BDNF, delays photoreceptor loss in this hereditary retinal 
      degeneration. Repeated injections maintain the protective effect.
FAU - Chong, N H
AU  - Chong NH
AD  - Department of Pathology, Institute of Ophthalmology, University College London, 
      United Kingdom.
FAU - Alexander, R A
AU  - Alexander RA
FAU - Waters, L
AU  - Waters L
FAU - Barnett, K C
AU  - Barnett KC
FAU - Bird, A C
AU  - Bird AC
FAU - Luthert, P J
AU  - Luthert PJ
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 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Ciliary Neurotrophic Factor)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Nerve Tissue Proteins)
RN  - A3VLQ7024W (axokine)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Cataract/chemically induced
MH  - Cats
MH  - Cell Count/drug effects
MH  - Cell Survival/drug effects/physiology
MH  - *Ciliary Neurotrophic Factor
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Injections
MH  - Nerve Tissue Proteins/*pharmacology
MH  - Photoreceptor Cells, Vertebrate/cytology/*drug effects/*physiology
MH  - Retina/pathology
MH  - Retinal Degeneration/*genetics/pathology/*physiopathology
MH  - Retinitis Pigmentosa/pathology/physiopathology
EDAT- 1999/05/11 00:00
MHDA- 1999/05/11 00:01
CRDT- 1999/05/11 00:00
PHST- 1999/05/11 00:00 [pubmed]
PHST- 1999/05/11 00:01 [medline]
PHST- 1999/05/11 00:00 [entrez]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 1999 May;40(6):1298-305.