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Suppression of trkB expression by antisense oligonucleotides alters a neuronal phenotype in the rod pathway of the developing rat retina.

Publication ,  Journal Article
Rickman, DW; Bowes Rickman, C
Published in: Proc Natl Acad Sci U S A
October 29, 1996

trkB is the high-affinity receptor for brain-derived neurotrophic factor (BDNF), a trophic molecule with demonstrated effects on the survival and differentiation of a wide variety of neuronal populations. In the mammalian retina, trkB is localized to both ganglion cells and numerous cells in the inner nuclear layer. Much information on the role of BDNF in neuronal development has been derived from the study of trkB- and BDNF-deficient mutant mice. This includes an attenuation of the numbers of cortical neurons immunopositive for the calcium-binding proteins, parvalbumin, and calbindin. Unfortunately, these mutant animals typically fail to survive for > 24-48 hr after birth. Since most retinal neuronal differentiation occurs postnatally, we have devised an alternative scheme to suppress the expression of trkB in the retina to examine the role of BDNF on the postnatal development of neurons of the inner retina. Neonatal rats were treated with intraocular injection of an antisense oligonucleotide (1-2 microliters of 10-100 microM solution) targeted to the trkB mRNA. Immunohistochemistry with a polyclonal antibody to trkB showed that the expression of trkB in retinal neurons was suppressed 48-72 hr following a single injection. Northern blot analysis demonstrated that antisense treatment had no effect on the level of trkB mRNA, even after multiple injections. This suggests an effect of trkB antisense treatment on protein translation, but not on RNA transcription. No alterations were observed in the thickness of retinal cellular or plexiform layers, suggesting that BDNF is not the sole survival factor for these neurons. There were, however, alterations in the patterns of immunostaining for parvalbumin, a marker for the narrow-field, bistratified AII amacrine cell-a central element of the rod (scotopic) pathway. This was evidenced by a decrease in both the number of immunostained somata (> 50%) and in the intensity of immunolabeling. However, the immunostaining pattern of calbindin was not affected. These studies suggest that the ligands for trkB have specific effects on the neurochemical phenotypic expression of inner retinal neurons and in the development of a well-defined retinal circuit.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

October 29, 1996

Volume

93

Issue

22

Start / End Page

12564 / 12569

Location

United States

Related Subject Headings

  • S100 Calcium Binding Protein G
  • Retina
  • Receptors, Nerve Growth Factor
  • Receptor, trkB
  • Receptor Protein-Tyrosine Kinases
  • Rats
  • Phenotype
  • Parvalbumins
  • Oligonucleotides, Antisense
  • Neurons
 

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Rickman, D. W., & Bowes Rickman, C. (1996). Suppression of trkB expression by antisense oligonucleotides alters a neuronal phenotype in the rod pathway of the developing rat retina. Proc Natl Acad Sci U S A, 93(22), 12564–12569. https://doi.org/10.1073/pnas.93.22.12564
Rickman, D. W., and C. Bowes Rickman. “Suppression of trkB expression by antisense oligonucleotides alters a neuronal phenotype in the rod pathway of the developing rat retina.Proc Natl Acad Sci U S A 93, no. 22 (October 29, 1996): 12564–69. https://doi.org/10.1073/pnas.93.22.12564.
Rickman, D. W., and C. Bowes Rickman. “Suppression of trkB expression by antisense oligonucleotides alters a neuronal phenotype in the rod pathway of the developing rat retina.Proc Natl Acad Sci U S A, vol. 93, no. 22, Oct. 1996, pp. 12564–69. Pubmed, doi:10.1073/pnas.93.22.12564.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

October 29, 1996

Volume

93

Issue

22

Start / End Page

12564 / 12569

Location

United States

Related Subject Headings

  • S100 Calcium Binding Protein G
  • Retina
  • Receptors, Nerve Growth Factor
  • Receptor, trkB
  • Receptor Protein-Tyrosine Kinases
  • Rats
  • Phenotype
  • Parvalbumins
  • Oligonucleotides, Antisense
  • Neurons