title: Minocycline attenuates photoreceptor degeneration in a mouse model of subretinal hemorrhage microglial: inhibition as a potential therapeutic strategy.
abstract: Hemorrhage under the neural retina (subretinal hemorrhage) can occur in the context of age-related macular degeneration and induce subsequent photoreceptor cell death and permanent vision loss. Current treatments with the objective of removing or displacing the hemorrhage are invasive and of mixed efficacy. We created a mouse model of subretinal hemorrhage to characterize the inflammatory responses and photoreceptor degeneration that occur in the acute aftermath of hemorrhage. It was observed that microglial infiltration into the outer retina commences as early as 6 hours after hemorrhage. Inflammatory cells progressively accumulate in the outer nuclear layer concurrently with photoreceptor degeneration and apoptosis. Administration of minocycline, an inhibitor of microglial activation, decreased microglial expression of chemotactic cytokines in vitro and reduced microglial infiltration and photoreceptor cell loss after subretinal hemorrhage in vivo. Inflammatory responses and photoreceptor atrophy occurred after subretinal hemorrhage, however, the degree of response and atrophy were similar between C3-deficient and C3-sufficient mice, indicating a limited role for complement-mediated processes. Our data indicate a role for inflammatory responses in driving photoreceptor cell loss in subretinal hemorrhage, and it is proposed that microglial inhibition may be beneficial in the treatment of subretinal hemorrhage.
authors.affiliation: Unit on Neuron-Glia Interactions in Retinal Diseases, Office of the Scientific Director, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Lian
authors.initials: L
authors.lastname: Zhao
authors.forename: Wenxin
authors.initials: W
authors.lastname: Ma
authors.forename: Robert N
authors.initials: RN
authors.lastname: Fariss
authors.forename: Wai T
authors.initials: WT
authors.lastname: Wong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects*; D008911:Minocycline / Q000494:pharmacology*; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects*; D012166:Retinal Hemorrhage / Q000473:pathology / Q000517:prevention & control*; D012173:Retinitis / Q000378:metabolism / Q000473:pathology; D057135:Wet Macular Degeneration / Q000473:pathology / Q000517:prevention & control*
chemical_list: D015815:Cell Adhesion Molecules; D018925:Chemokines; D016207:Cytokines; D008911:Minocycline