Neuronal migration and glial remodeling in degenerating retinas of aged rats and in nonneovascular AMD

Invest Ophthalmol Vis Sci. 2003 Feb;44(2):856-65. doi: 10.1167/iovs.02-0416.


Purpose: To demonstrate structural and immunocytochemical changes associated with light-induced degeneration in albino rat retinas and human AMD retinas.

Methods: Retinas from Wistar rats aged 3, 6, or 10 months were examined by immunocytochemistry, with antibodies to neuronal and glial markers. Results were compared with human nonneovascular AMD retinas.

Results: In aging rat retinas, many photoreceptors were lost in response to normal ambient light exposure. Photoreceptor loss was preceded by loss of RPE cells. Müller cells extended processes through gaps in Bruch's membrane, into the choroid. immunolabeling for gamma-aminobutyric acid (GABA), the glycine transporter Glyt-1, and the rod bipolar cell marker PKC revealed the presence of numerous neuronal somata and processes that appeared to have migrated into the choroidal region. Processes of presumptive ganglion cells remodeled and stratified in the choroid, where strong labeling for synaptic vesicle antigens was present. Myelination of retinal ganglion cell axons was also observed, especially in the peripheral retina. In AMD retinas, glial rearrangement and displacement of neurons suggestive of their migration were also observed.

Conclusions: In response to loss of RPE and photoreceptor cells, adult retinal neurons migrate out of the retina along remodeled processes of Müller cells. The presence of synaptic vesicle antigens suggests the formation of new synapses between migrating neurons. The myelination is probably due to the ingress of Schwann cells from the sclera. The presence of some similar changes in human AMD retinas suggests that these findings are of broad significance for determining the likely events in transplantation of neurons in the human retina and elsewhere.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems, Neutral / metabolism
  • Animals
  • Biomarkers / analysis
  • Cell Movement
  • Glycine Plasma Membrane Transport Proteins
  • Humans
  • Macular Degeneration / metabolism
  • Macular Degeneration / pathology*
  • Male
  • Neuroglia / pathology*
  • Neurons / pathology*
  • Protein Kinase C / metabolism
  • Radiation Injuries, Experimental / etiology
  • Radiation Injuries, Experimental / metabolism
  • Radiation Injuries, Experimental / pathology*
  • Rats
  • Rats, Wistar
  • Retina / metabolism
  • Retina / pathology
  • Retina / radiation effects*
  • Retinal Degeneration / etiology
  • Retinal Degeneration / metabolism
  • Retinal Degeneration / pathology*
  • gamma-Aminobutyric Acid / metabolism


  • Amino Acid Transport Systems, Neutral
  • Biomarkers
  • Glycine Plasma Membrane Transport Proteins
  • SLC6A9 protein, human
  • Slc6a9 protein, rat
  • gamma-Aminobutyric Acid
  • Protein Kinase C