Cells of the human optic nerve head express glial cell line-derived neurotrophic factor (GDNF) and the GDNF receptor complex

Mol Vis. 2003 Jun 16;9:249-56.

Abstract

Purpose: Glial cell-line derived neurotrophic factor (GDNF) is a distant member of the TGFbeta family of growth factors and has wide ranging effects within the central nervous system. In the present study we profile the expression of GDNF and its receptor complex (Ret and GFRalpha-1) in cells isolated from the human optic nerve head (ONH).

Methods: Lamina cribrosa (LC) cells and ONH astrocytes were used from normal donors of various ages. Total RNA was isolated and subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) to examine mRNA expression of GDNF, Ret, and GFRalpha-1. Western immunoblotting and immunohistochemistry was used to study protein expression of GDNF and GDNF receptor complex proteins in cultured ONH cells. An immunoassay system (ELISA) was used to examine secretion of GDNF by ONH cells. Cell proliferation was examined following exogenous administration of GDNF.

Results: Lamina cribrosa cells, ONH astrocytes, and LC tissues expressed messenger RNA for GDNF, Ret and GFRalpha-1. Lamina cribrosa cells and ONH astrocytes also expressed protein for GDNF, Ret, and GFRalpha-1. Secretion of GDNF by either cell type was not detected. Exogenous GDNF caused a significant increase in cell proliferation of LC cells but not ONH astrocytes.

Conclusions: Cells from the human lamina cribrosa express mRNA and protein for GDNF and its receptor complex. LC cells proliferate in response to exogenous GDNF. The potential for autocrine and/or paracrine GDNF signaling thus exists within the lamina cribrosa, a tissue involved in glaucoma pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Blotting, Western
  • Cell Division / drug effects
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Fluorescent Antibody Technique, Indirect
  • Glial Cell Line-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Humans
  • Infant
  • Infant, Newborn
  • Middle Aged
  • Nerve Growth Factors / genetics*
  • Nerve Growth Factors / metabolism
  • Nerve Growth Factors / pharmacology
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism
  • Optic Disk / cytology*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-ret
  • RNA / isolation & purification
  • RNA, Messenger / biosynthesis
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • GDNF protein, human
  • GFRA1 protein, human
  • Glial Cell Line-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Nerve Growth Factors
  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Recombinant Proteins
  • RNA
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • Receptor Protein-Tyrosine Kinases