Li Z Y, Wong F, Chang J H, Possin D E, Hao Y, Petters R M, Milam A H
Department of Ophthalmology, University of Washington, Seattle 98195-6485, USA.
Invest Ophthalmol Vis Sci. 1998 Apr;39(5):808-19.
To further characterize the retinas of Pro3471Leu rhodopsin transgenic pigs, a model for human retinitis pigmentosa.
Retinas from normal and transgenic pigs, newborn to 20 months old, were processed for light and electron microscopic immunocytochemical examination.
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.
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.
进一步描述Pro3471Leu视紫红质转基因猪的视网膜特征，该猪是人类色素性视网膜炎的一种模型。
对出生至20个月大的正常猪和转基因猪的视网膜进行光镜和电镜免疫细胞化学检查。
出生时，转基因视网膜中的视杆细胞数量正常，但其外节短且排列紊乱，内节含有视紫红质阳性膜堆叠。新生视杆细胞突触缺乏突触小泡和突触带，并有许多视紫红质阳性的丝状伪足样突起，延伸超过锥体细胞突触进入外网状层。视杆细胞死亡在2周时明显，6周时在中周部和中央区域明显。远周边视杆细胞最初保存较好，但到9个月时几乎所有视杆细胞都已退化。锥体细胞退化比视杆细胞慢，但4周时锥体细胞突触萎缩，一些中周部锥体细胞对磷酸二酯酶γ、抑制蛋白和恢复蛋白失去免疫反应性。从9个月到20个月，锥体细胞外节逐渐缩短，更多锥体细胞对这些蛋白质失去免疫反应性。
视紫红质转基因猪视网膜与人类色素性视网膜炎视网膜具有许多细胞学特征，并提供了一个研究光感受器退化最早阶段的机会，而这在人类中知之甚少。新生视杆细胞中视紫红质定位异常的发现与突变视紫红质错误路由作为导致视杆细胞死亡的早期过程一致。光感受器突触的新变化可能与这些视网膜早期的电生理异常相关。
