Phosphodiesterase 6β Expression In Developing Mouse Retina

Saint Louis University, St. Louis, Missouri 63103, USA

The rd1 mouse is a well-studied model of retinitis pigmentosa (RP), an inherited retinal
degenerative disease affecting approximately 1 in 4000 people. It is characterized by a mutation
in the Pde6b gene that codes for Phosphodiesterase 6β (PDE6β), a downstream effector of
phototransduction. Pde6b gene expression occurs embryonically in mouse retina, whereas other
proteins involved in phototransduction are expressed around postnatal day 5 (P5). The primary
aim of this study is to investigate the temporal and spatial expression pattern of PDE6β protein
during photoreceptor development. Using Western blots with wild type and rd1 mouse retinas
from P2 – P21 we demonstrated that PDE6β protein is expressed in wild type retinas by P2 and
is not detected in rd1 retinas. The earliest detection of PDE6β in wild type retinas by
immunohistochemistry was at P6, where it was confined to the apical region of the photoreceptor
layer. The expression of PDE6β protein prior to differentiation of photoreceptor cells and prior to
expression of other phototransduction proteins is consistent with the hypothesis that PDE6β may
play a role during photoreceptor development distinct from its role in phototransduction. Our lab
previously showed that Prenylated Rab Acceptor 1 (PRA1), a vesicular trafficking protein, is
downregulated in the developing rd1 retina, although its function in the retina is unknown. The
second aim of this study was to explore the relationship between PRA1 and PDE6β. We used
immunohistochemistry to determine whether the two proteins are co-localized during the
postnatal differentiation period. However, no co-localization between PDE6β and PRA1 was
detected. The function of PRA1 in developing retina remains to be elucidated.

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