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V. M. Maggio, A. M. Richmond, J. G. Martak, S. C. E. Hoge, A. Y. Chowdhury, J. M. Ogilvie; Rabac1 is Differentially Localized in Developing rd1 Compared to Wild Type Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4308.
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© ARVO (1962-2015); The Authors (2016-present)
The rd1 mouse is a well studied model of retinal degeneration. During early postnatal development and prior to degeneration (postnatal days P4-P8), pathology consistent with defects in vesicular trafficking has been reported (Blanks et al., 1974; Caley et al., 1972; Sanyal and Bal, 1973). In microarray analysis of wild-type (wt) and rd1 retinas at P2-P8, Rab acceptor 1 (Rabac1) was the only identified gene, other than the mutant PDE6b, to be downregulated at all time points (Ogilvie et al., 2006). Rabac1 acts as a GDI dissociation factor to facilitate transfer of cytosolic GDP-bound Rab to the membrane during vesicular trafficking. Here, we investigate the distribution of Rabac1 protein in postnatal wt and rd1 mouse retinas.
Eyecups from wt and rd1 age-matched littermates were harvested at developmental ages between birth and P21. Tissue was fixed, cryoprotected and processed for immunohistochemistry using an antibody against Rabac1 and double labeled with the cis-Golgi marker, GM130. Images were obtained using a Zeiss LSM 510 Meta confocal microscope.
In wt retinas at all ages examined, Rabac1-like immunoreactivity (LIR) is associated with Golgi and the perinuclear region of most inner retinal cells. Punctate labeling is also seen throughout both plexiform layers. A similar pattern of Rabac1-LIR is seen in the rd1 inner retina at all ages. At P21, intense Rabac1-LIR is observed in photoreceptor inner segments (IS), where Golgi membranes reside, and in outer segments with no staining in the outer nuclear layer (ONL). The P10 wt retina shows intense Rabac1-LIR in developing IS with the Golgi neatly aligned at the IS margin. Some Rabac1-LIR is also seen in the ONL associated with Golgi. Mislocalization of the Golgi and Rabac1-LIR is observed in the rd1 retina at P10. Prior to P10, few differences were observed in the staining pattern between wt and rd1 retinas, although less Rabac1-LIR is observed in the rd1 retina.
Together, our data suggests that a decrease in Rabac1 expression may correlate with disruption of Golgi and vesicular trafficking prior to photoreceptor cell death in rd1 mouse retina.
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