Early loss of synaptic protein PSD-95 from rod terminals of rhodopsin P347L transgenic porcine retina.
Retinitis pigmentosa (RP), a type of retinal degeneration involving first rod and then slow cone photoreceptor degeneration, can be caused by any of a number of mutations in different genes. In the cases of mutations affecting rod-specific genes such as rhodopsin, it is unclear how the mutations may cause degeneration of cones. We have used the porcine retina, which is rod-dominated and has an abundance of cones, to study the mutation-induced changes in both rod and cone photoreceptors. Like patients with the same mutation, rhodopsin P347L transgenic swine manifest rod-cone degeneration. In addition, the rod bipolar cells fail to form synaptic connections with rods; instead, they form ectopic synapses with cones. The mechanisms that prevent the formation of the rod-rod bipolar cell synaptic connection are not known. We used specific antibodies and immunocytochemistry to show that the synaptic protein, PSD-95, is present in both normal and transgenic porcine retinas. During neonatal development, however, PSD-95 is lost from rod terminals in the transgenic swine. This loss is virtually complete (90%) by postnatal day 5, at a time when greater than 80% of rod cell bodies still remain. Furthermore, the remaining rods retain their outer segments and their gross morphology appears relatively normal. In contrast, PSD-95 expression continues in cone terminals, even in 10-month-old transgenic swine, where the rods have all disappeared and the cones show signs of severe degeneration. These results suggest that loss of PSD-95 may not be a general consequence of the deteriorating cell. Rather, the very early and selective loss of PSD-95 from the rod terminals may be causally related to the absence of rod-rod bipolar cell synapses in the rhodopsin P347L transgenic retina.
Blackmon
S M
SM
Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA.
Peng
Y W
YW
Hao
Y
Y
Moon
S J
SJ
Oliveira
L B
LB
Tatebayashi
M
M
Petters
R M
RM
Wong
F
F
D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D000906:Antibodies; D004195:Disease Models, Animal; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012243:Rhodopsin / Q000235:genetics*; D013552:Swine; D013569:Synapses / Q000737:chemistry / Q000378:metabolism*
D000906:Antibodies; D009419:Nerve Tissue Proteins; C033652:postsynaptic density proteins; D012243:Rhodopsin