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A. Romeo Caffé, Annika K. Söderpalm, Inger Holmqvist, Theo van Veen; A Combination of CNTF and BDNF Rescues rd Photoreceptors but Changes Rod Differentiation in the Presence of RPE in Retinal Explants. Invest. Ophthalmol. Vis. Sci. 2001;42(1):275-282.
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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
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