Local Microglial Activation Induced and Labeled in the Retina in a Novel Subretinal Hemorrhage Mouse Model

Subretinal hemorrhage (SRH) is caused by the accumulation of blood between the neurosensory retina and the retinal pigment epithelium or between the retinal pigment epithelium and the choroid. It often arises from age-related macular degeneration, traumas, and may occur spontaneously caused by other diseases like hypertension and diabetes. Here, we developed a novel technique by co-injection of blood and a dye-coupled tracer protein, Cholera toxin subunit B (CtB), to better localize and understand the disease and how it can cause microglial activation, inflammation, and partial vision loss. Our results show that microglia are activated in the inner retinal regions and also in the zones neighboring the blood injection. In contrast, the non-affected zone of the affected eye showed no microglial activation. Based on the results, we provide evidence of inner retinal microglial activation and the appearance of microglia and macrophages in the pigment epithelium. Using advanced imaging techniques, we were able to localize better the affected area that comprises not only the retinal area over the blood clot but the neighboring regions as well. These findings will provide the basis for novel therapeutic interventions targeting neuroinflammation in the retina after subretinal hemorrhage and other diseases affecting the eye.