title: Inhibition of LPS-induced retinal microglia activation by naloxone does not prevent photoreceptor death.
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.
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, 83 Fen Yang Road, Shanghai, 200031, People's Republic of China.
authors.forename: Xiaoshuang
authors.initials: X
authors.lastname: Jiang
authors.forename: Yingqin
authors.initials: Y
authors.lastname: Ni
authors.forename: Tianjin
authors.initials: T
authors.lastname: Liu
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Ren
authors.forename: Gezhi
authors.initials: G
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D018920:Coculture Techniques; D007249:Inflammation; D053583:Interleukin-1beta / Q000096:biosynthesis; D008070:Lipopolysaccharides; D017628:Microglia / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology* / Q000187:drug effects; D012162:Retinal Degeneration / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D009270:Naloxone