Soluble adenylyl cyclase is required for retinal ganglion cell and photoreceptor differentiation

Peter X. Shaw, Jiahua Fang, Alan Sang, Yan Wang, Michael S Kapiloff, Jeffrey L. Goldberg

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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 Math5cre/sACfl/fl and Chx10cre/sACfl/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 Chx10cre/sACfl/fl and Math5cre/sACfl/fl mice, but this reduction and abnormal morphology persisted in the adults in only the Chx10cre/sACfl/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.

Original languageEnglish (US)
Pages (from-to)5083-5092
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume57
Issue number11
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

Fingerprint

Retinal Ganglion Cells
Adenylyl Cyclases
Cell Differentiation
Amacrine Cells
Stem Cells
Nerve Fibers
Genetic Recombination
Fluorescent Antibody Technique
Axons
Retina
Cell Survival
Growth

Keywords

  • Amacrine cell
  • Photoreceptors
  • Retinal development
  • Retinal ganglion cell
  • Soluble adenylyl cyclase

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Soluble adenylyl cyclase is required for retinal ganglion cell and photoreceptor differentiation. / Shaw, Peter X.; Fang, Jiahua; Sang, Alan; Wang, Yan; Kapiloff, Michael S; Goldberg, Jeffrey L.

In: Investigative Ophthalmology and Visual Science, Vol. 57, No. 11, 01.09.2016, p. 5083-5092.

Research output: Contribution to journalArticle

Shaw, Peter X. ; Fang, Jiahua ; Sang, Alan ; Wang, Yan ; Kapiloff, Michael S ; Goldberg, Jeffrey L. / Soluble adenylyl cyclase is required for retinal ganglion cell and photoreceptor differentiation. In: Investigative Ophthalmology and Visual Science. 2016 ; Vol. 57, No. 11. pp. 5083-5092.
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N2 - 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 Math5cre/sACfl/fl and Chx10cre/sACfl/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 Chx10cre/sACfl/fl and Math5cre/sACfl/fl mice, but this reduction and abnormal morphology persisted in the adults in only the Chx10cre/sACfl/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.

AB - 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 Math5cre/sACfl/fl and Chx10cre/sACfl/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 Chx10cre/sACfl/fl and Math5cre/sACfl/fl mice, but this reduction and abnormal morphology persisted in the adults in only the Chx10cre/sACfl/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.

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