Anterograde degeneration along the visual pathway after optic nerve injury

PLoS One. 2012;7(12):e52061. doi: 10.1371/journal.pone.0052061. Epub 2012 Dec 26.


Purpose: To investigate anterograde degenerative changes along the visual pathway in a rat model of optic nerve axotomy.

Methods: Optic nerve transection was performed in adult Sprague-Dawley rats. Animals were sacrificed at regular time intervals and tissues harvested. Immunoblotting followed by densitometric analysis was used to determine the phosphorylation profile of Akt in the dorsal lateral geniculate nucleus (dLGN) and the primary visual cortex (V1). The neuronal cell size and cell density were measured in the dLGN and the V1 using Nissl staining. The prevalence of apoptosis was characterized by terminal deoxynucleotidyl-transferase-mediated biotin-dUTP nick end labelling (TUNEL) histochemistry. Caspase-3 antibodies were also used to identify apoptotic cells. Neurons and astrocytes were detected using NeuN and glial fibrillary acidic protein (GFAP), respectively.

Results: An early and sustained loss of Akt phosphorylation was observed after optic nerve transection in both dLGN and V1. At week one, a decrease in the neuronal cell size (50.5±4.9 vs 60.3±5.0 µm(2), P = 0.042) and an increase of TUNEL positive cells (7.9±0.6 vs 1.4±0.5 ×10(2) cells/mm(2), P<0.001) were evident in the dLGN but not in V1. A significant decline in neuronal cell number (14.5±0.1 vs 17.4±1.3 ×10(2) cells/mm(2), P = 0.048), cell size (42.5±4.3 vs 62.1±4.7 µm(2), P = 0.001) and an increase in apoptotic cells (5.6±0.5 vs 2.0±0.4 ×10(2) cells/mm(2), P<0.001) appeared in V1 initially at one month post-transection. The changes in the visual pathway continued through two months. Both neuronal cells and GFAP-positive glial cells were affected in this anterograde degeneration along the visual pathway.

Conclusions: Anterograde degeneration along the visual pathway takes place in target relay (LGN) and visual cortex following the optic nerve injury. Apoptosis was observed in both neural and adjacent glial cells. Reduction of Akt phosphorylation preceded cellular and apoptotic changes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Astrocytes / pathology*
  • Axonal Transport
  • Geniculate Bodies / pathology*
  • Male
  • Nerve Degeneration*
  • Optic Nerve Injuries / pathology*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Visual Cortex / pathology*
  • Visual Pathways / pathology*


  • Proto-Oncogene Proteins c-akt

Grant support

Supported by Ophthalmic Research Institute Australia (ORIA), National Multiple Sclerosis Society (NMSS), Multiple Sclerosis Research Australia (MSRA Incubator Grant, 10-057), and Macquarie University New Staff (MQNS) Grant. AK was supported by the Sydney Foundation for Medical Research. VG was supported by an educational grant from Allergan Australia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.