Interleukin-10 protects retinal ganglion cell from laser induced ocular hypertension in the rat glaucoma model

Abstract

Immune response or inflammatory factors can be beneficial or detrimental to neurons in the central nervous system (CNS). It is a major issue in neuroscience of how we can make use of the beneficial inflammatory factors against neurodegeneration. In an ocular hypertension (OH) model that mimic glaucoma, mild and chronic neurodegeneration of retinal ganglion cells (RGCs) occurs. This experimental model provides us an opportunity to examine effects of cytokines on neurons under chronic stress. We hypothesize that Th2-inflammatory cytokines provide neuroprotective effects on RGCs under OH. Therefore, we aim to investigate the biological effects of interleukin-10 (IL-10) as an anti-inflammatory cytokine on RGCs. By using OH as an experimental glaucoma model, intravitreous injection of IL-10 afforded neuroprotection on RGCs. The effects were surprisingly long-lasting for four weeks by one single injection. Elevated expression levels of insulin-like growth factor-1 (IGF-1) was shown to be one possible neuroprotective mechanism of IL-10 treatment in vivo under OH. In addition, increased immunoreactivity of pAkt (Ser473) was found in RGCs under IL-10 treatment. By using in vitro primary cortical neuronal cultures, IL-10 was proved to directly induce expression of IGF-1 in neurons. Furthermore, intravitreous injection of IL-10 was found to modulate the morphology of retinal microglia under OH. Taken together, our study has proved that Th2-inflammatory factor such as IL-10 provided neuroprotective effects modulating neurons as well as microglia. The study may provide an alternative neuroprotective strategy for glaucoma patients in future.