Abstract
Purpose: :
In the zebrafish retina, little is known about the changes that occur in second order neurons in response to photoreceptor degeneration. The goal of this study was to use zebrafish genetic models that result in specific loss of rods, cones, or both, in order to examine the morphological alterations occurring in the bipolar cells.
Methods: :
Two photoreceptor degeneration lines were used in this study; the XOPS-mCFP transgenic line causes rod degeneration (Morris et al. 2005), and the pde6c mutant line results in cone degeneration (Stearns et al. 2007). These lines were also intercrossed to create a zebrafish line exhibiting both, rod and cone degeneration. Bipolar cells were visualized either by immunolabeling for PKCα or by breeding each of the photoreceptor degeneration lines with the nyx::MYFP transgenic line, in which ON-bipolar cells express YFP (Shroeter et al. 2006). Immunohistochemistry was also used to label photoreceptors, and confocal microscopy was utilized to quantify changes in bipolar cell morphology.
Results: :
Retinas exhibiting cone photoreceptor degeneration show changes in ON-bipolar cell morphology compared to wild type retinas. Features affected include dendritic processes, axon terminal stratification, and localization of the cell body. Specifically, dendrites in retinas with photoreceptor degeneration often extended into the photoreceptor cell layer, showing longer processes that what is observed in the wild type retina. Additionally, axon terminals were seen to extend beyond the inner plexiform layer, reaching and terminating within the ganglion cell layer. In contrast, rod degeneration resulted in subtle alterations of bipolar cell morphology, particularly in the axon terminals.
Conclusions: :
These data indicate that maintaining normal bipolar cell morphology in the zebrafish retina is more dependent on intact and functional cone photoreceptors than on intact rod photoreceptors. Further studies are proposed to investigate the developmental process of individual bipolar cells in response to photoreceptor degeneration. Insight into the integrity of second order neurons following photoreceptor cell degeneration will directly benefit our understanding of cell transplantation strategies aimed at restoring vision.
Keywords: retina: distal (photoreceptors, horizontal cells, bipolar cells) • degenerations/dystrophies • genetics