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Peter Shaw, Jiahua Fang, Alan Sang, Yan Wang, Lonny Levin, Jochen Buck, Michael Kapiloff, Jeffrey L Goldberg; Soluble adenylyl cyclase is required for retinal ganglion cell and photoreceptor differentiation. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
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.
sAC was conditionally deleted during early retinal development using Math5 and Chx10 promoter-driven Cre-Lox recombination. Retinal neuron numbers were quantified by immunofluorescence using cell type-specific markers in newborn and adult mice and after optic nerve injury in the adult.
We found that the adult RGC numbers in wild-type, sACfl/fl/Math5-Cre+ and sACfl/fl/Chx10-Cre+ groups were 150.61 ± 17.89, 129.66 ± 13.65, 99.55 ± 20.29 (mean ± standard deviation) cells/μm, respectively; and the thickness of β-tubulin stained axons in wild-type, sACfl/fl/Math5-Cre+ and sACfl/fl/Chx10-Cre+ groups were 11.02 ± 2.37, 2.18 ± 0.79, 1.53 ± 0.89 cells/μm, respectively. We also observed similar reduction of RGC and axon in newborn mice. The thickness of photoreceptor layer was slightly but statistically significantly decreased in both newborn sACfl/fl/Math5-Cre+mice and sACfl/fl/Chx10-Cre+ (WT 38.4 ± 6.2 v.s. Math5/sAC cKO 29.3 ± 5.4 v.s. Chx10/sAC cKO 13.7 ± 2.8 μm), but this reduction only persisted in the adult in sACfl/fl/Chx10-Cre+ mice (WT 126.69 ± 13.41 v.s. Math5/sAC cKO 122.40 ± 8.86 v.s Chx10/sAC cKO 106.08 ± 13.19 μm). Optic nerve injury decreased RGC survival in sACfl/fl/Chx10-Cre+ mice more than in wild-type control mice. The RGC cell numbers were 2386.25 ± 361.53 and 2049 ± 360.41 cells/mm2 of in wild-type group and sACfl/fl/Chx10-Cre+ group, respectively in animals without optic nerve crush. After crush injury, the RGC numbers were greatly reduced (901.25 ± 130.11 and 579.37 ± 129.67 cells/mm2, respectively in wild-type and sACfl/fl/Chx10-Cre+ groups)
sAC plays an important role in the development of RGCs and photoreceptors, and contributes to RGC survival after optic nerve injury.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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