SOCS3 regulates pathological retinal angiogenesis through modulating SPP1 expression in microglia and macrophages

Area of Science:

• Immunology
• Ophthalmology
• Molecular Biology

Background:

• Pathological ocular angiogenesis involves myeloid cell activation.
• Mechanisms of immune-vascular crosstalk in ocular neovascularization are not fully understood.

Purpose of the Study:

• To elucidate the role of suppressor of cytokine signaling 3 (SOCS3) in myeloid cells during ocular neovascularization.
• To identify molecular pathways regulating immune cell involvement in pathological angiogenesis.

Main Methods:

• Utilized mouse models of ocular angiogenesis.
• Performed single-cell RNA sequencing to analyze gene expression in myeloid cells.
• Investigated the SOCS3/STAT3/SPP1 signaling axis.
• Examined the effects of pharmaceutical interventions targeting SOCS3 and SPP1.

Main Results:

• Absence of SOCS3 in myeloid cells increased microglia and macrophage accumulation during neovascularization.
• Identified secreted phosphoprotein 1 (Spp1) as highly expressed in these myeloid cells, particularly in SOCS3-deficient models.
• Confirmed Spp1 as a transcriptional target of signal transducer and activator of transcription 3 (STAT3).
• Pharmaceutical activation of SOCS3 or blocking of SPP1 significantly reduced pathological neovascularization.

Conclusions:

• The SOCS3/STAT3/SPP1 axis is a critical regulator of pathological retinal angiogenesis.
• Targeting this axis offers a potential therapeutic strategy for treating ocular neovascular diseases.