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Inhibition of LPS-induced retinal microglia activation by naloxone does not prevent photoreceptor death
Xiaoshuang Jiang1, Yingqin Ni, Tianjin Liu
1Department of Ophthalmology, Eye and ENT Hospital of Fudan University, 83 Fen Yang Road, Shanghai, 200031, People's Republic of China.
Abstract:
Microglia-associated inflammation is closely related to the pathogenesis of retinal degenerative disorders. We have previously shown in vivo that naloxone protected photoreceptors from light-induced apoptosis possibly through inhibiting microglial activation. In this study, we attempted to explore the effect of lipopolysaccharide (LPS)-activated microglia on photoreceptor death and the influence of naloxone treatment using an in vitro retinal microglia and 661 W photoreceptor co-culture system. Immunofluorescent staining and ELISA measurements demonstrated that LPS activated microglia by changing the morphology and increasing the production of proinflammatory factors interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. Flow cytometry analysis of annexin V/propidium iodide staining showed that LPS-activated microglia promoted the apoptosis of co-cultured 661 W photoreceptor cells. Naloxone inhibited microglial activation and decreased the release of IL-1beta and TNF-alpha but could not prevent photoreceptors from undergoing apoptosis. Considering the dual role of microglia-associated inflammation in both neurotoxicity and neuroprotection, modulating the function, rather than simply inhibiting their activation, might be a new therapeutic method for preventing photoreceptor degeneration.
Insights
Naloxone reduced microglial activation and inflammatory factors in a retinal co-culture model. However, it did not prevent photoreceptor cell death, suggesting functional modulation, not just inhibition, is key for treating retinal degeneration.
Area of Science:
- Neuroscience
- Immunology
- Ophthalmology
Background:
- Microglia-associated inflammation is implicated in retinal degenerative diseases.
- Previous in vivo studies suggested naloxone may protect photoreceptors by inhibiting microglial activation.
Purpose of the Study:
- To investigate the in vitro effect of lipopolysaccharide (LPS)-activated microglia on photoreceptor cell death.
- To evaluate the impact of naloxone treatment on this co-culture system.
Main Methods:
- Co-culture of retinal microglia and 661 W photoreceptor cells.
- Lipopolysaccharide (LPS) to activate microglia.
- Immunofluorescent staining, ELISA, and flow cytometry to assess microglial activation, cytokine production, and photoreceptor apoptosis.
- Naloxone treatment.
Main Results:
- LPS activated microglia, altering morphology and increasing interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) production.
- LPS-activated microglia promoted apoptosis in co-cultured 661 W photoreceptor cells.
- Naloxone inhibited microglial activation and reduced IL-1beta and TNF-alpha levels but did not prevent photoreceptor apoptosis.
Conclusions:
- Microglia-activated inflammation contributes to photoreceptor cell death in vitro.
- While naloxone inhibits microglial activation, it does not rescue photoreceptors from apoptosis in this model.
- Modulating microglial function, rather than solely inhibiting activation, may offer a novel therapeutic strategy for photoreceptor degeneration.
