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A Distinct Microglial Cell Population Expressing Both CD86 and CD206 Constitutes a Dominant Type and Executes
Yan Zhang1,2,3, Yong Soo Park1,2, In-Beom Kim1,2,3,4
1Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Abstract:
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 NaIO3-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.
Insights
Microglial cells in retinal degeneration (RD) do not fit the M1/M2 classification. Instead, they exhibit dual CD86/CD206 expression, indicating a role in phagocytosis, not inflammation.
Area of Science:
- Neuroscience
- Immunology
- Ophthalmology
Background:
- Microglial cells are key regulators of inflammation in retinal degeneration (RD).
- Conventional M1/M2 classification of microglia may not accurately reflect their function in the retina.
Purpose of the Study:
- To investigate the spatiotemporal changes and functional classification of microglial cells during induced retinal degeneration.
- To determine if M1/M2 markers accurately represent microglial function in RD.
Main Methods:
- Induced retinal degeneration in mice using blue-light and NaIO3.
- Immunolabeling for microglial markers (IBA1, P2RY12, CD86, CD206) and TUNEL assay for photoreceptor cell death.
- Flow cytometry and qRT-PCR to analyze microglial populations and gene expression (Il-10, Il-6, Trem-2, Apoe, Lyz2).
Main Results:
- Photoreceptor cell death was observed from 24 to 72 hours post-induction.
- Microglial marker P2RY12 decreased while CD86 increased at 24 hours.
- At 72 hours, CD86/CD206 double-labeled microglia were dominant and showed increased expression of Apoe, Trem2, and Lyz2, but not Il-6 or Il-10.
Conclusions:
- Microglial cells in active retinal degeneration cannot be classified as strictly M1 or M2.
- The majority of microglia in RD express both CD86 and CD206.
- These dual-expressing microglia are primarily involved in phagocytosis rather than classical inflammation.

