Abstract
Purpose: :
Cone bipolar cells, the essential backbone of the cone pathways, constitute a very large population of the second order neurons that receive inputs from photoreceptors in the outer retina and synapse onto ganglion cells and amacrine cells in the inner retina. When photoreceptors die, bipolar cells are left without their major source of input. Can they manage to survive and remain intact? Due to a lack of specific molecular markers and technical inaccessibility to the inner retinal neurons, we know little about the morphology and light response properties of the cone bipolar cells in disease conditions and during aging. In this study, we will investigate the morphlogical and physiological properties of cone bipolar cells in rd1 mice, the mouse model of retinitis pigmentosa.
Methods: :
In order to follow and investigate the degeneration of cone bipolar cells, we backcrossed GUS8.4-GFP mice, one of transgenic mice in which cone bipolar cells of type 7 express green fluorescent protein (GFP), into rd1 mice. The resulting mouse line was used to study the time course and topography of the cone bipolar cell death, and to examine whether the axons and dendrites of the cone bipolar cells develop normally and how they respond to the initial photoreceptor cell loss, using a combination of immunohistochemistry and confocal microscopy.
Results: :
The type 7 cone bipolar cells in the rd1 mouse retina undergo a negative remodeling during and after photoreceptor death. Cone bipolar cells retain their dendritic and axonal terminal shape until at least one month of age. Soon after that, the loss of bipolar cell dendrites, neurite sprouting, and soma displacement occurred. After loss of the dendrites, some cone bipolar cells maintain their monopolar morphology for many weeks, and then die over time. Surprisingly, one or more of the axonal processes could often be shown to contain synaptic ribbons, as visualized by antibodies against RIBEYE. However, compared with their counterparts in wild type, the density of synaptic ribbons in rd1 mice is dramatically reduced, and the size of synaptic ribbons is getting smaller.
Conclusions: :
Cone bipolar cells appear not immune to cell death and are vulnerable to insults caused by the loss of photoreceptors. It is not clear whether photoreceptors regulate directed dendritic and axonal growth of bipolar cells during development. However, it is clear that cone bipolar cells cannot maintain their normal morphology for too long without getting inputs from photoreceptors.
Keywords: retinal degenerations: cell biology • bipolar cells • microscopy: light/fluorescence/immunohistochemistry