Soluble Adenylyl Cyclase Is Required for Retinal Ganglion Cell and Photoreceptor Differentiation

PURPOSE: We have previously demonstrated that soluble adenylyl cyclase (sAC) is necessary for retinal ganglion cell (RGC) survival and axon growth. Here, we further investigate the role of sAC in neuronal differentiation during retinal development. METHODS: Chx10 or Math5 promoter-driven Cre-Lox recombination were used to conditionally delete sAC from early and intermediate retinal progenitor cells during retinal development. We examined cell type–specific markers expressed by retinal cells to estimate their relative numbers and characterize retinal laminar morphology by immunofluorescence in adult and newborn mice. RESULTS: Retinal ganglion cell and amacrine cell markers were significantly lower in the retinas of adult Math5(cre)/sAC(fl/fl) and Chx10(cre)/sAC(fl/fl) mice than in those of wild-type controls. The effect on RGC development was detectable as early as postnatal day 1 and deleting sAC in either Math5- or Chx10-expressing retinal progenitor cells also reduced nerve fiber layer thickness into adulthood. The thickness of the photoreceptor layer was slightly but statistically significantly decreased in both the newborn Chx10(cre)/sAC(fl/fl) and Math5(cre)/sAC(fl/fl) mice, but this reduction and abnormal morphology persisted in the adults in only the Chx10(cre)/sAC(fl/fl) mice. CONCLUSIONS: sAC plays an important role in the early retinal development of RGCs as well as in the development of amacrine cells and to a lesser degree photoreceptors.