Rhodopsin transgenic pigs as a model for human retinitis pigmentosa.
OBJECTIVE
To further characterize the retinas of Pro3471Leu rhodopsin transgenic pigs, a model for human retinitis pigmentosa.


METHODS
Retinas from normal and transgenic pigs, newborn to 20 months old, were processed for light and electron microscopic immunocytochemical examination.


RESULTS
At birth, rod numbers were normal in the transgenic retinas, but their outer segments were short and disorganized and their inner segments contained stacks of rhodopsin-positive membranes. The newborn rod synapses lacked synaptic vesicles and ribbons and had numerous rhodopsin-positive, filopodia-like processes that extended past the cone synapses into the outer plexiform layer. Rod cell death was apparent by 2 weeks and was pronounced in the mid periphery and central regions by 6 weeks. Far peripheral rods were initially better preserved, but by 9 months virtually all rods had degenerated. Cones degenerated more slowly than rods, but by 4 weeks the cone synapses were shrunken and some mid peripheral cones had lost their immunoreactivity for phosphodiesterase-gamma, arrestin, and recoverin. From 9 months to 20 months, the cone outer segments shortened progressively, and more cones lost immunoreactivity for these proteins.


CONCLUSIONS
The rhodopsin transgenic pig retina shares many cytologic features with human retinas with retinitis pigmentosa and provides an opportunity to examine the earliest stages in photoreceptor degeneration, about which little is known in humans. The finding of abnormal rhodopsin localization in newborn rods is consistent with misrouting of mutant rhodopsin as an early process leading to rod cell death. Novel changes in the photoreceptor synapses may correlate with early electrophysiological abnormalities in these retinas.
Li
Z Y
ZY
Department of Ophthalmology, University of Washington, Seattle 98195-6485, USA.
Wong
F
F
Chang
J H
JH
Possin
D E
DE
Hao
Y
Y
Petters
R M
RM
Milam
A H
AH
D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics*; D000831:Animals, Newborn; D002452:Cell Count; D016923:Cell Death; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D010786:Photoreceptor Cells / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D012168:Retinal Pigments / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012243:Rhodopsin / Q000235:genetics* / Q000378:metabolism; D013552:Swine
D005136:Eye Proteins; D012168:Retinal Pigments; D012243:Rhodopsin