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

Overview

Journal Invest Ophthalmol Vis Sci

Specialty Ophthalmology

Date 2016 Sep 29

PMID 27679853

Citations 4

Authors

Peter X Shaw

Jiahua Fang

Alan Sang

Yan Wang

Michael S Kapiloff

Jeffrey L Goldberg

Affiliations

Soon will be listed here.

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.

Citing Articles

Compartmentalization of local cAMP signaling in neuronal growth and survival.

Boczek T, Kapiloff M Neural Regen Res. 2019; 15(3):453-454.

PMID: 31571655 PMC: 6921356. DOI: 10.4103/1673-5374.266055.

Pharmacological modulation of the CO/HCO/pH-, calcium-, and ATP-sensing soluble adenylyl cyclase.

Wiggins S, Steegborn C, Levin L, Buck J Pharmacol Ther. 2018; 190:173-186.

PMID: 29807057 PMC: 6484840. DOI: 10.1016/j.pharmthera.2018.05.008.

Intracellular compartmentation of cAMP promotes neuroprotection and regeneration of CNS neurons.

Cameron E, Kapiloff M Neural Regen Res. 2017; 12(2):201-202.

PMID: 28400794 PMC: 5361496. DOI: 10.4103/1673-5374.200797.

Role of cyclic AMP in the eye with glaucoma.

Shim M, Kim K, Ju W BMB Rep. 2016; 50(2):60-70.

PMID: 27916026 PMC: 5342868. DOI: 10.5483/bmbrep.2017.50.2.200.

References

Brzezinski 4th J, Prasov L, Glaser T . Math5 defines the ganglion cell competence state in a subpopulation of retinal progenitor cells exiting the cell cycle. Dev Biol. 2012; 365(2):395-413. PMC: 3337348. DOI: 10.1016/j.ydbio.2012.03.006. View

Watson R, Buck J, Levin L, Winger R, Wang J, Arase H . Endothelial CD99 signals through soluble adenylyl cyclase and PKA to regulate leukocyte transendothelial migration. J Exp Med. 2015; 212(7):1021-41. PMC: 4493416. DOI: 10.1084/jem.20150354. View

Polans A, Buczylko J, Crabb J, Palczewski K . A photoreceptor calcium binding protein is recognized by autoantibodies obtained from patients with cancer-associated retinopathy. J Cell Biol. 1991; 112(5):981-9. PMC: 2288874. DOI: 10.1083/jcb.112.5.981. View

Young R . Cell differentiation in the retina of the mouse. Anat Rec. 1985; 212(2):199-205. DOI: 10.1002/ar.1092120215. View

Fang J, Shaw P, Wang Y, Goldberg J . Krüppel-Like Factor 4 (KLF4) Is Not Required for Retinal Cell Differentiation. eNeuro. 2016; 3(1). PMC: 4770008. DOI: 10.1523/ENEURO.0117-15.2016. View

Hatakeyama J, Kageyama R . Retinal cell fate determination and bHLH factors. Semin Cell Dev Biol. 2004; 15(1):83-9. DOI: 10.1016/j.semcdb.2003.09.005. View

Liu I, Chen J, Ploder L, Vidgen D, van der Kooy D, Kalnins V . Developmental expression of a novel murine homeobox gene (Chx10): evidence for roles in determination of the neuroretina and inner nuclear layer. Neuron. 1994; 13(2):377-93. DOI: 10.1016/0896-6273(94)90354-9. View

Kunzevitzky N, Almeida M, Goldberg J . Amacrine cell gene expression and survival signaling: differences from neighboring retinal ganglion cells. Invest Ophthalmol Vis Sci. 2010; 51(7):3800-12. PMC: 2904021. DOI: 10.1167/iovs.09-4540. View

Cepko C, Austin C, Yang X, Alexiades M, Ezzeddine D . Cell fate determination in the vertebrate retina. Proc Natl Acad Sci U S A. 1996; 93(2):589-95. PMC: 40096. DOI: 10.1073/pnas.93.2.589. View

10.

Rutherford A, Dhomen N, Smith H, Sowden J . Delayed expression of the Crx gene and photoreceptor development in the Chx10-deficient retina. Invest Ophthalmol Vis Sci. 2004; 45(2):375-84. DOI: 10.1167/iovs.03-0332. View

11.

Zippin J, Chen Y, Nahirney P, Kamenetsky M, Wuttke M, Fischman D . Compartmentalization of bicarbonate-sensitive adenylyl cyclase in distinct signaling microdomains. FASEB J. 2002; 17(1):82-4. DOI: 10.1096/fj.02-0598fje. View

12.

Burmeister M, Novak J, Liang M, Basu S, Ploder L, Hawes N . Ocular retardation mouse caused by Chx10 homeobox null allele: impaired retinal progenitor proliferation and bipolar cell differentiation. Nat Genet. 1996; 12(4):376-84. DOI: 10.1038/ng0496-376. View

13.

Yang Z, Ding K, Pan L, Deng M, Gan L . Math5 determines the competence state of retinal ganglion cell progenitors. Dev Biol. 2003; 264(1):240-54. DOI: 10.1016/j.ydbio.2003.08.005. View

14.

Levine E, Green E . Cell-intrinsic regulators of proliferation in vertebrate retinal progenitors. Semin Cell Dev Biol. 2004; 15(1):63-74. DOI: 10.1016/j.semcdb.2003.09.001. View

15.

Polans A, Witkowska D, Haley T, Amundson D, Baizer L, Adamus G . Recoverin, a photoreceptor-specific calcium-binding protein, is expressed by the tumor of a patient with cancer-associated retinopathy. Proc Natl Acad Sci U S A. 1995; 92(20):9176-80. PMC: 40947. DOI: 10.1073/pnas.92.20.9176. View

16.

Buck J, Sinclair M, Schapal L, Cann M, Levin L . Cytosolic adenylyl cyclase defines a unique signaling molecule in mammals. Proc Natl Acad Sci U S A. 1999; 96(1):79-84. PMC: 15096. DOI: 10.1073/pnas.96.1.79. View

17.

Goldberg J, Espinosa J, Xu Y, Davidson N, Kovacs G, Barres B . Retinal ganglion cells do not extend axons by default: promotion by neurotrophic signaling and electrical activity. Neuron. 2002; 33(5):689-702. DOI: 10.1016/s0896-6273(02)00602-5. View

18.

Chen J, Martinez J, Milner T, Buck J, Levin L . Neuronal expression of soluble adenylyl cyclase in the mammalian brain. Brain Res. 2013; 1518:1-8. PMC: 3679342. DOI: 10.1016/j.brainres.2013.04.027. View

19.

Martinez J, Stessin A, Campana A, Hou J, Nikulina E, Buck J . Soluble adenylyl cyclase is necessary and sufficient to overcome the block of axonal growth by myelin-associated factors. J Neurosci. 2014; 34(28):9281-9. PMC: 4087207. DOI: 10.1523/JNEUROSCI.1434-14.2014. View

20.

Levin L, Buck J . Physiological roles of acid-base sensors. Annu Rev Physiol. 2014; 77:347-62. DOI: 10.1146/annurev-physiol-021014-071821. View