A Distinct Microglial Cell Population Expressing Both CD86 and CD206 Constitutes a Dominant Type and Executes Phagocytosis in Two Mouse Models of Retinal Degeneration

Microglial cells are the key regulators of inflammation during retinal degeneration (RD) and are conventionally classified as M1 or M2. However, whether the M1/M2 classification exactly reflects the functional classification of microglial cells in the retina remains debatable. We examined the spatiotemporal changes of microglial cells in the blue-LED and NaIO(3)-induced RD mice models using M1/M2 markers and functional genes. TUNEL assay was performed to detect photoreceptor cell death, and microglial cells were labeled with anti-IBA1, P2RY12, CD86, and CD206 antibodies. FACS was used to isolate microglial cells with anti-CD206 and CD86 antibodies, and qRT-PCR was performed to evaluate Il-10, Il-6, Trem-2, Apoe, and Lyz2 expression. TUNEL-positive cells were detected in the outer nuclear layer (ONL) from 24 h to 72 h post-RD induction. At 24 h, P2RY12 was decreased and CD86 was increased, and CD86/CD206 double-labeled cells occupied the dominant population at 72 h. And CD86/CD206 double-labeled cells showed a significant increase in Apoe, Trem2, and Lyz2 levels but not in those of Il-6 and Il-10. Our results demonstrate that microglial cells in active RD cannot be classified as M1 or M2, and the majority of microglia express both CD86 and CD206, which are involved in phagocytosis rather than inflammation.