Ciliary neurotrophic factor (CNTF)-mediated ganglion cell survival in a rodent model of non-arteritic anterior ischaemic optic neuropathy (NAION).

Abstract

BACKGROUND:

Ciliary neurotrophic factor (CNTF) has been shown to protect retinal ganglion cells (RGCs) in traumatic optic nerve injury. We sought to evaluate this neuroprotective effect of CNTF after an ischaemic event using rodent anterior ischaemic optic neuropathy (rAION), a mouse model of non-arteritic anterior ischaemic optic neuropathy (NAION).

METHODS:

We induced rAION in Thy1-cyan fluorescent protein (CFP) transgenic mice by exposing the optic nerve to frequency doubled neodymium yttrium aluminium garnet laser pulses following intravenous rose bengal injection. One day after rAION induction, an intravitreal injection of 0.75 μg CNTF or vehicle (sham injection) was given. Animals were euthanised on day 15 after induction, tissues isolated and CFP cells in the RGC layer were counted using stereology in flat-mounted retina. The average number of CFP-positive (CFP+) cells was determined for each study group and the percentages of RGC loss were compared between the different groups.

RESULTS:

Two weeks after rAION induction, significantly more (CFP+) cells were preserved in CNTF-treated eyes than in sham-injected controls. Sham-treated animals showed a 58% loss of CFP+ cells. In contrast, CFP+ cell density in CNTF-treated eyes decreased by only 10%, when compared with untreated control eyes. This increased survival was statistically significant (p<0.05).

CONCLUSIONS:

CNTF exerts a neuroprotective effect in ischaemic optic nerve injury and promotes RGC survival, suggesting that CNTF may be effective in the clinical treatment of human NAION.

• Authors: Michaela K Mathews, Yan Guo, Patricia Langenberg, Steven L Bernstein
• Journal: The British journal of ophthalmology (Br J Ophthalmol) Vol. 99 Issue 1 Pg. 133-7 (Jan 2015) ISSN: 1468-2079 [Electronic] England
• PMID: 25336580 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chemical References

• Ciliary Neurotrophic Factor
• Cyan Fluorescent Protein
• Neuroprotective Agents
• Green Fluorescent Proteins

Topics

• Animals
• Arteritis (drug therapy, pathology)
• Cell Count
• Cell Survival (physiology)
• Ciliary Neurotrophic Factor (therapeutic use)
• Disease Models, Animal
• Green Fluorescent Proteins (metabolism)
• Intravitreal Injections
• Male
• Mice
• Mice, Transgenic
• Neuroprotective Agents (therapeutic use)
• Optic Neuropathy, Ischemic (drug therapy, pathology)
• Retinal Ganglion Cells (pathology)