TrkB Receptor Signaling Regulates Developmental Death Dynamics, but Not Final Number, of Retinal Ganglion Cells

Overview

Journal J Neurosci

Specialty Neurology

Date 2003 Nov 7

PMID 14602830

Citations 17

Authors

Graeme S Pollock

Regine Robichon

Kristina A Boyd

Kristi A Kerkel

Melissa Kramer

Johnalyn Lyles

Ranjini Ambalavanar

Asema Khan

David R Kaplan

Robert W Williams

Douglas O Frost

Affiliations

Soon will be listed here.

Abstract

We investigated the effects of endogenous neurotrophin signaling on the death-survival of immature retinal ganglion cells (RGCs) in vivo. Null mutation of brain-derived neurotrophic factor [(BDNF) alone or in combination with neurotrophin 4 (NT4)] increases the peak rate of developmental RGC death as compared with normal. Null mutation of NT4 alone is ineffective. Null mutation of the full-length trkB (trkBFL) receptor catalytic domain produces a dose-dependent increase in the peak RGC death rate that is negatively correlated with retinal levels of trkBFL protein and phosphorylated (activated) trkBFL. Depletion of target-derived trkB ligands by injection of trkB-Fc fusion protein into the superior colliculus increases the peak rate of RGC death compared with trkA-Fc-treated and normal animals. Adult trkBFL+/- mice have a normal number of RGCs, despite an elevated peak death rate of immature RGCs. Thus, target-derived BDNF modulates the dynamics of developmental RGC death through trkBFL activation, but BDNF/trkB-independent mechanisms determine the final number of RGCs.

Citing Articles

Implications of TORCH Diseases in Retinal Development-Special Focus on Congenital Toxoplasmosis.

de Campos V, Calaza K, Adesse D Front Cell Infect Microbiol. 2020; 10:585727.

PMID: 33194824 PMC: 7649341. DOI: 10.3389/fcimb.2020.585727.

Altered Brain Expression of Insulin and Insulin-Like Growth Factors in Frontotemporal Lobar Degeneration: Another Degenerative Disease Linked to Dysregulation of Insulin Metabolic Pathways.

Liou C, Tong M, Vonsattel J, de la Monte S ASN Neuro. 2019; 11:1759091419839515.

PMID: 31081340 PMC: 6535914. DOI: 10.1177/1759091419839515.

Glaucoma Pathogenesis and Neurotrophins: Focus on the Molecular and Genetic Basis for Therapeutic Prospects.

Chitranshi N, Dheer Y, Abbasi M, You Y, Graham S, Gupta V Curr Neuropharmacol. 2018; 16(7):1018-1035.

PMID: 29676228 PMC: 6120108. DOI: 10.2174/1570159X16666180419121247.

Role of BDNF/TrkB pathway in the visual system: Therapeutic implications for glaucoma.

Mysona B, Zhao J, Bollinger K Expert Rev Ophthalmol. 2017; 12(1):69-81.

PMID: 28751923 PMC: 5524151. DOI: 10.1080/17469899.2017.1259566.

Over-Expression of Ephrin-A5 in Mice Results in Decreasing the Size of Progenitor Pool through Inducing Apoptosis.

Noh H, Park S Mol Cells. 2015; 39(2):136-40.

PMID: 26674965 PMC: 4757801. DOI: 10.14348/molcells.2016.2245.

References

Watson F, Heerssen H, Moheban D, Lin M, Sauvageot C, Bhattacharyya A . Rapid nuclear responses to target-derived neurotrophins require retrograde transport of ligand-receptor complex. J Neurosci. 1999; 19(18):7889-900. PMC: 6782462. View

Bennett J, Zeiler S, Jones K . Patterned expression of BDNF and NT-3 in the retina and anterior segment of the developing mammalian eye. Invest Ophthalmol Vis Sci. 1999; 40(12):2996-3005. View

Kaplan D, Miller F . Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol. 2000; 10(3):381-91. DOI: 10.1016/s0959-4388(00)00092-1. View

Atwal J, Massie B, Miller F, Kaplan D . The TrkB-Shc site signals neuronal survival and local axon growth via MEK and P13-kinase. Neuron. 2000; 27(2):265-77. DOI: 10.1016/s0896-6273(00)00035-0. View

Bibel M, Barde Y . Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev. 2000; 14(23):2919-37. DOI: 10.1101/gad.841400. View

von Bartheld C, Johnson J . Target-derived BDNF (brain-derived neurotrophic factor) is essential for the survival of developing neurons in the isthmo-optic nucleus. J Comp Neurol. 2001; 433(4):550-64. DOI: 10.1002/cne.1159. View

Lotto R, Asavaritikrai P, Vali L, Price D . Target-derived neurotrophic factors regulate the death of developing forebrain neurons after a change in their trophic requirements. J Neurosci. 2001; 21(11):3904-10. PMC: 6207345. View

Pollock G, Vernon E, Forbes M, Yan Q, Ma Y, Hsieh T . Effects of early visual experience and diurnal rhythms on BDNF mRNA and protein levels in the visual system, hippocampus, and cerebellum. J Neurosci. 2001; 21(11):3923-31. PMC: 6762725. View

Rohrer B, LaVail M, Jones K, Reichardt L . Neurotrophin receptor TrkB activation is not required for the postnatal survival of retinal ganglion cells in vivo. Exp Neurol. 2001; 172(1):81-91. PMC: 6519927. DOI: 10.1006/exnr.2001.7795. View

10.

Frost D, Ma Y, Hsieh T, Forbes M, Johnson J . Developmental changes in BDNF protein levels in the hamster retina and superior colliculus. J Neurobiol. 2001; 49(3):173-87. DOI: 10.1002/neu.1073. View

11.

Thanos S, Bahr M, Barde Y, Vanselow J . Survival and Axonal Elongation of Adult Rat Retinal Ganglion Cells. Eur J Neurosci. 1989; 1(1):19-26. DOI: 10.1111/j.1460-9568.1989.tb00770.x. View

12.

Ernfors P, Merlio J, Persson H . Cells Expressing mRNA for Neurotrophins and their Receptors During Embryonic Rat Development. Eur J Neurosci. 1992; 4(11):1140-1158. DOI: 10.1111/j.1460-9568.1992.tb00141.x. View

13.

Harvey A, Robertson D . Time-course and extent of retinal ganglion cell death following ablation of the superior colliculus in neonatal rats. J Comp Neurol. 1992; 325(1):83-94. DOI: 10.1002/cne.903250108. View

14.

Oppenheim R . Cell death during development of the nervous system. Annu Rev Neurosci. 1991; 14:453-501. DOI: 10.1146/annurev.ne.14.030191.002321. View

15.

Williams M, Pinon L, Linden R, Pinto L . The pearl mutation accelerates the schedule of natural cell death in the early postnatal retina. Exp Brain Res. 1990; 82(2):393-400. DOI: 10.1007/BF00231258. View

16.

Harvey A, Robertson D, Cole K . Direct visualization of death of neurones projecting to specific targets in the developing rat brain. Exp Brain Res. 1990; 80(1):213-7. DOI: 10.1007/BF00228865. View

17.

Hofer M, Pagliusi S, Hohn A, Leibrock J, Barde Y . Regional distribution of brain-derived neurotrophic factor mRNA in the adult mouse brain. EMBO J. 1990; 9(8):2459-64. PMC: 552273. DOI: 10.1002/j.1460-2075.1990.tb07423.x. View

18.

Wetmore C, Ernfors P, Persson H, Olson L . Localization of brain-derived neurotrophic factor mRNA to neurons in the brain by in situ hybridization. Exp Neurol. 1990; 109(2):141-52. DOI: 10.1016/0014-4886(90)90068-4. View

19.

Rodriguez-Tebar A, Barde Y . Binding characteristics of brain-derived neurotrophic factor to its receptors on neurons from the chick embryo. J Neurosci. 1988; 8(9):3337-42. PMC: 6569431. View

20.

Johnson J, Barde Y, Schwab M, Thoenen H . Brain-derived neurotrophic factor supports the survival of cultured rat retinal ganglion cells. J Neurosci. 1986; 6(10):3031-8. PMC: 6568792. View