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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAEY000505-03
Application #
8737667
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2013
Total Cost
$212,753
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
Zip Code
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