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B. Lin, R. H. Masland; Remodeling of ON and OFF Cone Bipolar Cells in the rd1 Mouse. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4880. doi: https://doi.org/.
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Remodeling of inner retinal neurons in retinal degenerations has been studied in some detail, notably by Strettoi, Marc and colleagues (Marc et al., 2003). However, little is known about the structural modifications for cone bipolar cells, due to a lack of antibodies that might specifically label them. Here we applied a method that does not use immunocytochemistry to study the morphology of cone bipolar cells in the rd1 mouse model. We analyzed their morphology at various stages of disease progression.
Adeno-associated viral (AAV) vectors, carrying GFP under control of a CMV promoter, were subretinally injected into the eyes of rd1 mice at the ages of P14 days to 5 months. The whole morphology of cone bipolar cells was revealed by GFP fluorescence. In order to distinguish among rod bipolar cells and ON and OFF cone bipolar cells, retinal slices and whole mounts were also counterstained with either PKCα, recoverin or Goα antibodies. The images of cone bipolar cells were acquired by confocal microscopy.
After 1 to 4 weeks post-injection, many retinal bipolar cells were transduced and strongly expressed GFP protein. They come in a wide variety of sizes and shapes. One week after subretinal injection of AAV-GFP into the eyes of rd1 mice at the age of 14 days, we observed the loss of some cone bipolar cell dendrites and axonal terminals. The axons of some OFF cone bipolar cells and a few ON cone bipolars had even been translocated from IPL to INL. OFF cone bipolar cells seem to be more vulnerable than ON cone bipolar cells. Atrophy of dendrites and axonal processes in cone bipolar cells was more extensive at later stages of photoreceptor degeneration. Some cone bipolar cells sprouted axon-like neurites, while others lost all their dendritic and axonal processes.
Photoreceptor degeneration appears to trigger earlier and more aggressive damage in the morphology of cone bipolar cells than previously believed. Even at early stages of rod loss, some cone bipolar cells displayed structural anomalies; healthy photoreceptors may be required to ensure the normal development of cone bipolar cells. Photoreceptor intervention would have to be performed quite early to prevent secondary effects on some inner retinal neurons.
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