Gene microarray analysis of experimental glaucomatous retina from cynomologous monkey

Invest Ophthalmol Vis Sci. 2003 Oct;44(10):4347-56. doi: 10.1167/iovs.02-1032.

Abstract

Purpose: To systematically explore changes in gene expression in the retina of monkeys with laser-induced glaucoma and to validate the microarray data on eyes with experimental glaucoma.

Methods: Glaucoma was induced in the right eye of four monkeys by repeated argon laser photocoagulation of the trabecular meshwork. The left eye served as the control. Retinas were isolated from glaucomatous and control eyes 30 days after photocoagulation. Gene expression changes were analyzed by human microarray chips which displayed a total of 9182 elements including Expression Sequence Tag (EST) clones. Changes in the expression of some genes were further confirmed by real-time PCR analysis. Immunohistochemical studies to examine protein expression of some gene products were also done for several genes that showed up- or downregulation by the microarray analysis.

Results: Two eyes with mild glaucoma and two with severe glaucoma were produced. In the mild and severe glaucomatous retina, the number of upregulated genes was 45 and 18, and the number of downregulated genes was 17 and 21, respectively. The number of genes that were up- or downregulated was 0.7% of all the genes examined. The real-time PCR analysis confirmed expression changes of some genes found in the microarray analysis. Ceruloplasmin was one of the upregulated genes, and it was found by immunohistochemical analyses to be expressed in Müller cells.

Conclusions: Gene expression profiles in laser-induced glaucomatous monkey retinas were determined, and only a very small population of genes was up- or downregulated in glaucomatous eyes. Upregulation of ceruloplasmin protein was found in the Müller cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ceruloplasmin / metabolism
  • Disease Models, Animal
  • Eye Proteins / genetics*
  • Fluorescent Antibody Technique, Indirect
  • Gene Expression Profiling*
  • Glaucoma / genetics*
  • Glaucoma / metabolism
  • Glial Fibrillary Acidic Protein / metabolism
  • Intraocular Pressure
  • Laser Coagulation
  • Macaca fascicularis
  • Oligonucleotide Array Sequence Analysis*
  • Retina / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trabecular Meshwork / surgery
  • Up-Regulation

Substances

  • Eye Proteins
  • Glial Fibrillary Acidic Protein
  • Ceruloplasmin