Early loss of synaptic protein PSD-95 from rod terminals of rhodopsin P347L transgenic porcine retina

Brain Res. 2000 Dec 1;885(1):53-61. doi: 10.1016/s0006-8993(00)02928-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Animals, Newborn
  • Antibodies
  • Disease Models, Animal
  • Nerve Tissue Proteins / analysis
  • Nerve Tissue Proteins / immunology
  • Nerve Tissue Proteins / metabolism*
  • Retinal Rod Photoreceptor Cells / chemistry
  • Retinal Rod Photoreceptor Cells / metabolism*
  • Retinal Rod Photoreceptor Cells / pathology
  • Retinitis Pigmentosa / genetics
  • Retinitis Pigmentosa / metabolism
  • Retinitis Pigmentosa / pathology
  • Rhodopsin / genetics*
  • Swine
  • Synapses / chemistry
  • Synapses / metabolism*


  • Antibodies
  • Nerve Tissue Proteins
  • postsynaptic density proteins
  • Rhodopsin