A few
days after axonal injury, the associated retinal ganglion cells (RGCs) begin to
degenerate. This is especially so if the injury is close to the eye.
The death
of RGCs can be prevented almost completely by overexpression of the
antiapoptotic Bcl family proteins, such as, Bcl-2 and Bcl-xL.
However,
the regeneration and survival of axons is also dependent on numerous
intracellular signaling pathways. This is seen when RGCs overexpressing Bcl-2
or Bcl-xL fail to regenerate axons, unless provided with additional growth
factors.
A number
of trophic factors can slow, but not completely stop, the death of RGCs. These
factors include ciliary neurotrophic factor (CNTF), brain derived
neurotrophic factor (BDNF), neurotrophin 4/5 nerve growth
factor, insulin-like growth factor-1, granulocyte colony-stimulating
factor, glial-derived neurotrophic factor, and neurturin.
The death
of axotomized RGCs is also slowed by preventing caspase cleavage, blocking
the nuclear enzyme poly (adenosine diphosphate–ribose) polymerase (a substrate
for caspases), blocking nitric oxide synthase, introducing reducing
agents, or inhibiting cell death via caspase-independent
pathways. Long-term prevention of RGC death after axotomy may require the
development of long-term delivery systems or a combination of treatments.
Fibroblast
growth factor 2 stimulates some axon regeneration through the optic nerve.
Two
molecules present in the eye were found to stimulate mature RGCs to regenerate
their axons. One is mannose, a simple sugar that is abundant in the vitreous.
Mannose stimulates RGCs to extend moderately long axons if cells have
sufficiently high levels of intracellular cyclic adenosine monophosphate
(cAMP). The second growth factor is oncomodulin (Ocm), a 12-kDa,
calcium-binding protein secreted by macrophages.
The
advances during the past few years give hope for the possibility that at least
some RGCs will be able to regenerate their axons all the way to their central
targets. The future challenges will include finding ways to optimize this
regeneration and testing whether they restore functionally meaningful levels of
vision.
REFERENCE:
Benowitz
LI, Yin Y. Optic Nerve Regeneration. Arch Ophthalmol. 2010;128(8):1059–1064.
doi:10.1001/archophthalmol.2010.152
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