Neuroprotective Effects of Omega-3 Polyunsaturated Fatty Acids in a Rat Model of Anterior Ischemic Optic Neuropathy

Invest Ophthalmol Vis Sci. 2017 Mar 1;58(3):1603-1611. doi: 10.1167/iovs.16-20979.

Abstract

Purpose: The purpose of this study was to investigate the therapeutic effect of omega-3 polyunsaturated fatty acid (ω-3 PUFA) administration in a rat model of anterior ischemic optic neuropathy (rAION).

Methods: The level of blood arachidonic acid/eicosapentaenoic acid (AA/EPA) was measured to determine the suggested dosage. The rAION-induced rats were administered fish oil (1 g/day EPA) or phosphate-buffered saline (PBS) by daily gavage for 10 consecutive days to evaluate the neuroprotective effects.

Results: Blood fatty acid analysis showed that the AA/EPA ratio was reduced from 17.6 to ≤1.5 after 10 days of fish oil treatment. The retinal ganglion cell (RGC) densities and the P1-N2 amplitude of flash visual-evoked potentials (FVEP) were significantly higher in the ω-3 PUFA-treated group, compared with the PBS-treated group (P < 0.05). The number of apoptotic cells in the RGC layer of the ω-3 PUFA-treated rats was significantly decreased (P < 0.05) compared with that of the PBS-treated rats. Treatment with ω-3 PUFAs reduced the macrophage recruitment at the optic nerve (ON) by 3.17-fold in the rAION model. The M2 macrophage markers, which decrease inflammation, were induced in the ω-3 PUFA-treated group in contrast to the PBS-treated group. In addition, the mRNA levels of tumor necrosis factor-alpha, interleukin-1 beta, and inducible nitric oxide synthase were significantly reduced in the ω-3 PUFA-treated group.

Conclusions: The administration of ω-3 PUFAs has neuroprotective effects in rAION, possibly through dual actions of the antiapoptosis of RGCs and anti-inflammation via decreasing inflammatory cell infiltration, as well as the regulation of macrophage polarization to decrease the cytokine-induced injury of the ON.

MeSH terms

  • Animals
  • Apoptosis
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Evoked Potentials, Visual / drug effects
  • Fatty Acids, Omega-3 / administration & dosage*
  • Fatty Acids, Omega-3 / pharmacokinetics
  • Immunohistochemistry
  • Male
  • Optic Nerve / drug effects
  • Optic Nerve / pathology*
  • Optic Nerve / physiopathology
  • Optic Neuropathy, Ischemic / blood
  • Optic Neuropathy, Ischemic / drug therapy*
  • Optic Neuropathy, Ischemic / physiopathology
  • Rats
  • Rats, Wistar
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / pathology*

Substances

  • Fatty Acids, Omega-3