Image defocus modulates activity of bipolar and amacrine cells in macaque retina

Invest Ophthalmol Vis Sci. 2004 Jul;45(7):2065-74. doi: 10.1167/iovs.03-1046.


Purpose: To demonstrate regulation of ocular growth and refractive development by image quality and processing in the retina in higher primates. Focus-sensitive retinal neurons were labeled with immunocytochemical markers after briefly altering image quality in infant monkeys.

Methods: Six rhesus monkeys (Macaca mulatta) 20- to 30-days-old were fitted with goggles after 6 hours in the light. Three wore a +3 D lens and three a diffuser on the treated eye; contralateral control eyes wore plano lenses matched in transmission to the goggles on treated eyes. After 30, 60, or 240 minutes exposure, the animals were killed, the eyes opened and fixed in 4% formaldehyde, and cryosections labeled with antibodies to inducible activity markers (transcription factors Egr-1 and Fra-2) and type-specific amacrine cell markers. Labeled cells were identified and counted in a fluorescence microscope, and the spatial density of activity-labeled nuclei and the frequency of activity-labeling of specific amacrine cells were determined, without knowing treated eye or duration.

Results: Focus-sensitive immunoreactivity was demonstrated for Egr-1 and Fra-2 in a GAD65-immunoreactive (IR) subpopulation of GABAergic amacrine cells, and for Egr-1 alone in PKC alpha-, 115A10-, and CD15-IR ON-bipolar cells. Activity of ON-bipolar and GABAergic amacrine cells, as indicated by Egr-1 induction, was stimulated more by in-focus or myopically-defocused images than by hyperopically-defocused or diffusely blurred images, regardless of exposure duration.

Conclusions: This was the first evidence of focus-dependent activation of bipolar as well as amacrine cells in a primate retina. Focus-sensitive neurons are candidates for roles in vision-dependent regulation of eye growth.

Publication types

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

MeSH terms

  • Amacrine Cells / cytology*
  • Amacrine Cells / metabolism
  • Animals
  • Biomarkers / analysis
  • DNA-Binding Proteins / metabolism
  • Fos-Related Antigen-2
  • Glutamate Decarboxylase / metabolism
  • Immediate-Early Proteins / metabolism
  • Interneurons / cytology*
  • Interneurons / metabolism
  • Isoenzymes / metabolism
  • Macaca mulatta
  • Microscopy, Fluorescence
  • Refractive Errors / physiopathology*
  • Retina / physiopathology*
  • Transcription Factors / metabolism
  • gamma-Aminobutyric Acid / metabolism


  • Biomarkers
  • DNA-Binding Proteins
  • Fos-Related Antigen-2
  • Immediate-Early Proteins
  • Isoenzymes
  • Transcription Factors
  • gamma-Aminobutyric Acid
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2