mmalian “1446712 RP model The results of Q344X suggest that the ADCY plays a role in photoreceptor cell death in human RP. However, we still doubted that the phenomenon occurs only in fish. So we used a more common RP rodent model, rd10 mice. Mislocalized rhodopsin is also reported in rd10 mice. Mice homozygous for “2674416 the rd10 mutation show histological changes at postnatal day 16. Rd10 mice have a point mutation in exon 13 of beta PDE and ectopic rhodopsin is found in the IS in photoreceptor cells. Rd10 mice have less PDE protein than the wild-type in the retina. We suspected that mislocalized phototransduction easily occurs in the Rd10 retina, but actually, photoreceptor degeneration depends on light exposure. We applied SQ22536, an adenylyl cyclase inhibitor, to rd10 mice. A 10 mM/ 2 mL solution of SQ22536 was injected into the vitreous of one April 2012 | Volume 7 | Issue 4 | e32472 Mislocalized Phototransduction Causes Cell Death eye. We injected 2 ml PBS into the other eye as a control. The thickness of the retinal outer nuclear layer was measured at 6 retinal points in each eye, and we calculate average of 6 points CVT-3146 cost thicknesses. We injected SQ22536 or PBS at P18 and 
sectioned at P28. At 10 mM, SQ 22536 increased the ONL thickness by 29% in the rd10 mice retina. The thickness of the ONL in the rd10 mouse retina of the SQ22536 treated group significantly increased, compared with the control group. However, it did not affect the thickness of the inner nuclear layer in the retina of the SQ22536 treated group, compared to the control group. The ONL/INL ratio of the SQ22536 treated retina increased compared to the control retina in rd10 mice. The results using ovl, Q344X transgenic, and rd10 mice indicate that adenylyl cyclase may be commonly involved the photoreceptor cell death pathway in human retinitis pigmentosa. April 2012 | Volume 7 | Issue 4 | e32472 Mislocalized Phototransduction Causes Cell Death Discussion In the eye, the photoreceptor is the light detector, and the relationship between light and photoreceptor death has been discussed. RP is a slow progressive disease and most patients are concerned about light exposure accelerating the progression of the disease. Hao et al. revealed that, in a mutant mouse model, phototransduction has an apparent relationship to photoreceptor cell death. They also reported that photoreceptor cell death is caused by even relatively low-level light exposure, which is not harmful for wild-type photoreceptors. The cell death mechanism is different from that caused by strong light exposure in the RP retina, but the details are not yet known. In photoreceptor cell death in rhodopsin mutant, some investigators suggest that transducin is involved, and the others suggest not. Our results of genetic manipulation and antagonist experiments prefer the former hypothesis in rod photoreceptor cell death caused by relatively low-level light exposure. In our experiment, PDE does not affect the rod photoreceptor cell death in ovl. However, it is possible that the knockdown of PDE causes rod generation in mammals. So we April 2012 | Volume 7 | Issue 4 | e32472 Mislocalized Phototransduction Causes Cell Death could not conclude that PDE is not involved in photoreceptor cell death caused by light, however, our results suggest that transducin is included in rod photoreceptor cell death caused by light. Alfinito first proposed that ADCY is related to photoreceptor cell death, however, they used digested and unhealthy salamand