The life, death and regenerative ability of immature and mature rat retinal ganglion cells are influenced by their birthdate

Elizabeth J. Dallimore, Kevin Park, Margaret A. Pollett, Jeremy S H Taylor, Alan R. Harvey

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The extensive period of retinal ganglion cell (RGC) neurogenesis in the rat is associated with a protracted sequence of arrival of their axons into central targets such as the superior colliculus (SC) (Dallimore et al., 2002). Using in utero 5-bromo-2'-deoxyrudine (BrdU) injections to label early (embryonic day (E) 15) or late (E18 or E19) born RGCs, we now show that E15 RGCs with axons that enter the SC prenatally undergo programmed cell death earlier than late-born RGCs whose axons only reach the SC late in the first postnatal week. These late-born RGCs do not begin to die until postnatal day (P) 5/6. Removal of retrograde trophic support by P1 SC ablation initially only affects E15 RGCs; however by P5 death of late-born RGCs is increased, confirming that a switch to target dependency is delayed in this cohort. In a further experiment it was found that, following complete rostral SC transection at P2, the proportion of post-lesion axons originating from E19 RGCs was significantly greater than the proportion that normally makes up the retinotectal projection. Thus, even in neonatal brain, uninjured late-arriving axons are more likely to grow across a lesion site than injured axons undergoing regeneration. To study if birth date also affects regenerative potential in adulthood, autologous peripheral nerve (PN) was grafted onto the cut optic nerve in mature BrdU labelled rats. We found that, compared to E15 RGCs, a significantly greater proportion of late-born RGCs survived axotomy, but comparatively fewer of these surviving E19 RGCs regrew an axon into a graft. In summary, this research shows that the birthdate of RGCs significantly impacts on their subsequent life history and response to injury. Understanding how developing central nervous system (CNS) neurons acquire dependency on target-derived trophic support may lead to new strategies for enhancing survival and regeneration in adult CNS.

Original languageEnglish
Pages (from-to)353-365
Number of pages13
JournalExperimental Neurology
Volume225
Issue number2
DOIs
StatePublished - Oct 1 2010
Externally publishedYes

Fingerprint

Retinal Ganglion Cells
Axons
Superior Colliculi
Regeneration
Central Nervous System
Axotomy
Neurogenesis
Optic Nerve
Peripheral Nerves
Cell Death
Parturition
Transplants
Neurons
Injections
Wounds and Injuries
Brain
Research

Keywords

  • Axonal regeneration
  • Neurogenesis
  • Peripheral nerve graft
  • Plasticity
  • Programmed cell death
  • Rat visual system
  • Retina
  • Superior colliculus
  • Target factors

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

The life, death and regenerative ability of immature and mature rat retinal ganglion cells are influenced by their birthdate. / Dallimore, Elizabeth J.; Park, Kevin; Pollett, Margaret A.; Taylor, Jeremy S H; Harvey, Alan R.

In: Experimental Neurology, Vol. 225, No. 2, 01.10.2010, p. 353-365.

Research output: Contribution to journalArticle

Dallimore, Elizabeth J. ; Park, Kevin ; Pollett, Margaret A. ; Taylor, Jeremy S H ; Harvey, Alan R. / The life, death and regenerative ability of immature and mature rat retinal ganglion cells are influenced by their birthdate. In: Experimental Neurology. 2010 ; Vol. 225, No. 2. pp. 353-365.
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