Abstract
Purpose: :
The rd1 mouse retina is a model of early onset retinitis pigmentosa. A mutation in the beta-subunit of the rod-specific cGMP-phosphodiesterase causes cGMP accumulation in the retina, resulting in degeneration of the rod photoreceptors by one month of age in vivo or in organ culture. The molecular cascade that induces apoptosis remains poorly understood. We have previously shown that dopamine depletion blocks the degeneration of photoreceptors in the rd1 retinal organ culture model (Neurobiol Disease 2002, 10:33-40). Here we determine whether dopamine signaling regulates cGMP levels in the retinal organ culture model to protect photoreceptors.
Methods: :
Retinas were dissected from wild type (wt) and rd1 mice at postnatal day (P)2 and grown in organ culture in control media or in media with 6-OHDA in order to deplete dopamine. Organ cultures were harvested under dark conditions after 8 - 16 days in vitro. An ELISA assay was used to determine the concentration of cGMP for each sample.
Results: :
The concentration of cGMP in rd1 retinal organ cultures treated with 6-OHDA is significantly lower than in untreated control rd1 retinal organ cultures. However, treatment of retinal organ cultures with 6-OHDA does not reduce cGMP concentration to wt levels.
Conclusions: :
We have shown that dopamine depletion in rd1 retinal organ cultures reduces cGMP accumulation, which likely contributes to photoreceptor protection. Our results illustrate a role for dopamine signaling in regulation of cGMP, suggesting a novel dopamine signaling pathway in differentiating rod photoreceptors.
Keywords: photoreceptors • dopamine • retinal degenerations: cell biology