2. Academic Validation
  3. Ameboid Microglia as a Scavenger Role in Phagocytosis of Photoreceptor Outer Segment in an Experimental Retinal Detachment Model

Ameboid Microglia as a Scavenger Role in Phagocytosis of Photoreceptor Outer Segment in an Experimental Retinal Detachment Model

  • Invest Ophthalmol Vis Sci. 2025 Mar 3;66(3):4. doi: 10.1167/iovs.66.3.4.
Manjing Cao 1 2,  Yahan Zhang 1 2,  Yan Li 3,  Xian Zhang 4,  Mingming Ma 1 2
Affiliations

Affiliations

  • 1 Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China.
  • 3 Precision Research Center for Refractory Disease, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4 Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
PMID: 40035728 DOI: 10.1167/iovs.66.3.4
Abstract

Purpose: Photoreceptor (PR) death is the ultimate cause of irreversible vision loss in retinal detachment (RD). Previous studies have shown that microglia may have a dual role in RD. Nevertheless, the potential protective effects of microglia on PR are largely unknown. We aimed to uncover the phagocytic role of microglia in RD and propose a new concept to regulate PR survival.

Methods: An RD model was conducted by injecting sodium hyaluronate into the subretinal space (SRS) of C57BL/6J wild type mice. Bioinformatics analysis was used to evaluate the highly enriched pathways and terms relating to phagocytosis in human datasets and mouse transcriptomes of RD. The observation of microglial morphology was performed by immunofluorescence through cryosection and flat mount. PLX 3397 was used for microglial ablation. Phagocytosis of the outer segment (OS) by microglia was confirmed by immunofluorescence and hematoxylin and eosin staining. Expression of phagocytic markers in microglia was detected by immunofluorescence of cryosection. The PR survival was measured by TUNEL assay and hematoxylin and eosin staining. The optical coherence tomography (OCT) images through the center of the fovea in twelve patients were obtained to observe the clinic features of IS/OS dynamics after RD.

Results: The results showed that OS went through an accumulation-clearance process after RD. Ameboid microglia accumulated in the SRS and engulfed OS. Upregulation of phagocytic markers was observed in subretinal microglia. Depletion of microglia led to failure of OS clearance and retinal ruffling, which had the same characteristics as outer retinal undulation (ORU) in some patients with RD. PR did not benefit from microglial depletion, as no morphology and thickness recovery of PR was observed in the long term.

Conclusions: These results elucidate that microglial phagocytosis of OS is a critical process after RD. Insufficient phagocytosis leads to the accumulation of OS in the SRS and PR abnormalities. Appropriate regulation of microglial phagocytosis to remove OS may be a new concept to regulate photoreceptor survival.

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