Chonnam Med J.  2012 Aug;48(2):116-122. 10.4068/cmj.2012.48.2.116.

The Effect of Melatonin on Retinal Ganglion Cell Survival in Ischemic Retina

• Park SW
• Lee HS
• Sung MS
• Kim SJ

• KMID: 2172213
• DOI: http://doi.org/10.4068/cmj.2012.48.2.116

Abstract

Our objective was to determine whether melatonin increases retinal ganglion cell (RGC) survival in ischemic mouse retina. Transient retinal ischemia was induced by an acute elevation of intraocular pressure in C57BL/6 mice. To evaluate the effect of melatonin on retinal ischemia, an equal amount of either melatonin or vehicle was intraperitoneally injected into the mice 1 hour before ischemia, at the time of ischemia, and 1 hour after ischemia. Hypoxia inducible factor 1alpha (HIF-1alpha) and glial fibrillary acidic protein (GFAP) expression were assessed 6, 12, and 24 hours after ischemia-reperfusion by Western blot. RGC survival was measured 2 weeks after ischemia-reperfusion. The expression of HIF-1alpha and GFAP peaked 24 hours after ischemia-reperfusion in ischemic retina. The treatment of ischemic retina with melatonin resulted in the inhibition of increased expression of HIF-1alpha and GFAP. RGC survival was greater in retinas treated with melatonin than in retinas treated with vehicle 2 weeks after ischemia-reperfusion. On the basis of our results, we suggest that melatonin treatment increased RGC survival in ischemic mouse retina. The neuroprotective effect of melatonin is mediated by the inhibition of HIF-1alpha stabilization and reduced activity of glial cells in ischemic mouse retina.

Keyword

Glaucoma; Ischemia; Melatonin; Neuroprotection

MeSH Terms

Animals
Anoxia
Blotting, Western
Glaucoma
Glial Fibrillary Acidic Protein
Intraocular Pressure
Ischemia
Melatonin
Mice
Neuroglia
Neuroprotective Agents
Retina
Retinal Ganglion Cells
Retinaldehyde
Glial Fibrillary Acidic Protein
Melatonin
Neuroprotective Agents
Retinaldehyde

Figure

• 

  FIG. 1 Expression of HIF-1α and GFAP protein on ischemic mouse retina according to time interval. HIF-1α and GFAP expression was increased within 24 hours in ischemic mouse retina (A-C). Relative intensity of chemiluminescence for HIF-1α and GFAP protein bands was normalized using actin as a calibrator. *Significant at p<0.05 compared with control mouse retina. †Significant at p<0.05 compared with ischemic mouse retina-6 h, Error bars, SD. HIF-1α: hypoxia inducible factor 1α, GFAP: glial fibrillay acidic protein.

• 

  FIG. 2 The effect of melatonin on HIF-1α expression in ischemic mouse retina. Melatonin treatment significantly decreased HIF-1α protein expression in ischemic retina at 24 hours (A, B). Relative intensity of chemiluminescence for HIF-1α protein band was normalized using actin as a calibrator. *Significant at p<0.05 compared with control mouse retina. †Significant at p<0.05 compared with ischemic mouse retina-24 h. Error bars, SD. HIF-1α: hypoxia inducible factor 1α.

• 

  FIG. 3 The effect of melatonin on GFAP expression in ischemic mouse retina. Melatonin treatment significantly decreased GFAP protein expression in ischemic retina at 24 hours (A, B). Relative intensity of chemiluminescence for GFAP protein band was normalized using actin as a calibrator. Error bars, SD. *Significant at p<0.05 compared with control mouse retina. †Significant at p<0.05 compared with ischemic mouse retina-24 h. Error bars, SD. GFAP: glial fibrillay acidic protein.

• 

  FIG. 4 The effect of melatonin on RGC survival in ischemic mouse retina. The retinal flat mounts of control (A), vehicle-treated ischemic retina (B) and melatonin-treated ischemic retina (C). The quantitative analysis of RGC survival (D). *Significant at p<0.05 compared with control mouse retina. †Significant at p<0.05 compared with ischemic mouse retina treated with saline. Error bars, SD. Scale bars, 100 µm.

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