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.

National Institute of Health (NIH)
National Eye Institute (NEI)
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U.S. National Eye Institute
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Zabel, Matthew K; Zhao, Lian; Zhang, Yikui et al. (2016) Microglial phagocytosis and activation underlying photoreceptor degeneration is regulated by CX3CL1-CX3CR1 signaling in a mouse model of retinitis pigmentosa. Glia 64:1479-91
Ma, Wenxin; Wong, Wai T (2016) Aging Changes in Retinal Microglia and their Relevance to Age-related Retinal Disease. Adv Exp Med Biol 854:73-8
Indaram, Maanasa; Ma, Wenxin; Zhao, Lian et al. (2015) 7-Ketocholesterol increases retinal microglial migration, activation, and angiogenicity: a potential pathogenic mechanism underlying age-related macular degeneration. Sci Rep 5:9144
Karlstetter, Marcus; Scholz, Rebecca; Rutar, Matt et al. (2015) Retinal microglia: just bystander or target for therapy? Prog Retin Eye Res 45:30-57
Wang, Minhua; Wang, Xu; Zhao, Lian et al. (2014) Macroglia-microglia interactions via TSPO signaling regulates microglial activation in the mouse retina. J Neurosci 34:3793-806
Wong, Wai T (2013) Microglial aging in the healthy CNS: phenotypes, drivers, and rejuvenation. Front Cell Neurosci 7:22
Cukras, Catherine A; Petrou, Philip; Chew, Emily Y et al. (2012) Oral minocycline for the treatment of diabetic macular edema (DME): results of a phase I/II clinical study. Invest Ophthalmol Vis Sci 53:3865-74
Roger, Jerome E; Ranganath, Keerthi; Zhao, Lian et al. (2012) Preservation of cone photoreceptors after a rapid yet transient degeneration and remodeling in cone-only Nrl-/- mouse retina. J Neurosci 32:528-41
Zhao, Lian; Ma, Wenxin; Fariss, Robert N et al. (2011) Minocycline attenuates photoreceptor degeneration in a mouse model of subretinal hemorrhage microglial: inhibition as a potential therapeutic strategy. Am J Pathol 179:1265-77