Abstract: Glaucoma results from irreversible loss of retinal ganglion cells (RGCs) through an unclear mechanism. Microglial polarization and neuroinflammation play an important role in retinal degeneration. Our study aimed to explore the function of microglial polarization during glaucoma progression and identify a strategy to alleviate retinal neuroinflammation. Retinal ischemia/reperfusion injury was induced in C57BL/6 mice. In a separate cohort of animals, interleukin (IL)-4 (50 ng/mL, 2 μL per injection) or vehicle was intravitreally injected after retinal ischemia/reperfusion injury. RGC loss was assessed by counting cells that were positive for the RGC marker RNA binding protein, mRNA processing factor in retinal flat mounts. The expression of classically activated (M1) and alternatively activated (M2) microglial markers were assessed by quantitative reverse transcription-polymerase chain reaction, immunofluorescence, and western blotting. The results showed that progressive RGC loss was accompanied by a continuous decrease in M2 microglia during the late phase of the 28-day period after retinal ischemia/reperfusion injury. IL-4 was undetectable in the retina at all time points, and intravitreal IL-4 administration markedly improved M2 microglial marker expression and ameliorated RGC loss in the late phase post-retinal ischemia/reperfusion injury. In summary, we observed that IL-4 treatment maintained a high number of M2 microglia after RIR and promoted RGC survival.

Key words: glaucoma, hyper-intraocular pressure, in vivo, interleukin-4, intravitreal injection, M2 microglia, neurodegeneration, neuroprotective effect, retinal ganglion cell, retinal ischemia-reperfusion