To determine how a progressive loss of photoreceptor cells
and the concomitant loss of glutamatergic input to second-order
neurons can affect inner-retinal signaling, glutamate receptor
expression was analyzed in the Royal College of Surgeons (RCS)
rat, an animal model of retinitis pigmentosa. Immunohistochemistry
was performed on retinal sections of RCS rats and congenic controls
between postnatal (P) day 3 and the aged adult (up to P350)
using specific antibodies against N-methyl-D-aspartate (NMDA)
subunits. All NMDA subunits (NR1, NR2A–2D) were expressed
in control and dystrophic retinas at all ages, and distinct
patterns of labeling were found in horizontal cells, subpopulations
of amacrine cells and ganglion cells, as well as in the outer
and inner plexiform layer (IPL). NR1 immunoreactivity in the
inner plexiform layer of adult control retinas was concentrated
in two distinct bands, indicating a synaptic localization of
NMDA receptors in the OFF and ON signal pathways. In the RCS
retina, these bands of NR1 immunoreactivity in the IPL were
much weaker in animals older than P40. In parallel, NR2B
immunoreactivity in the outer plexiform layer (OPL) of RCS rats
was always reduced compared to controls and vanished between
P40 and P120. The most striking alteration observed in the
degenerating retina, however, was a strong expression of NR1
immunoreactivity in Müller cell processes in the inner
retina which was not observed in control animals and which was
present prior to any visible sign of photoreceptor degeneration.
The results suggest functional changes in glutamatergic receptor
signaling in the dystrophic retina and a possible involvement
of Müller cells in early processes of this disease.
Retinochoroidal anastomoses in RCS rat eyes?
