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Updated: May 15, 2026
Quantification of Vascular Parameters in Whole Mount Retinas of Mice with Non-Proliferative and Proliferative Retinopathies
Published on: March 12, 2022
Macrophage metalloelastase (MMP-12) deficiency mitigates retinal inflammation and pathological angiogenesis in
Jingming Li1, Joshua J Wang, Qisheng Peng
1Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Abstract:
Pathological angiogenesis is a major cause of vision loss in ischemic and inflammatory retinal diseases. Recent evidence implicates macrophage metalloelastase (MMP-12), a macrophage-derived elastinolytic protease in inflammation, tissue remodeling and angiogenesis. However, little is known about the role of MMP-12 in retinal pathophysiology. The present study aims to explore the enzyme's contributions to retinal angiogenesis in oxygen-induced retinopathy (OIR) using MMP-12 knockout (KO) mice. We find that MMP-12 expression was upregulated in OIR, accompanied by elevated macrophage infiltration and increased inflammatory markers. Compared to wildtype mice, MMP-12 KO mice had decreased levels of adhesion molecule and inflammatory cytokines and reduced vascular leakage in OIR. Concomitantly, these mice had markedly reduced macrophage content in the retina with impaired macrophage migratory capacity. Significantly, loss of MMP-12 attenuated retinal capillary dropout in early OIR and mitigated pathological retinal neovascularization (NV). Similar results were observed in the study using MMP408, a pharmacological inhibitor of MMP-12. Intriguingly, in contrast to reducing pathological angiogenesis, lack of MMP-12 accelerated revascularization of avascular retina in OIR. Taken together, we conclude that MMP-12 is a key regulator of macrophage infiltration and inflammation, contributing to retinal vascular dysfunction and pathological angiogenesis.
Insights
Macrophage metalloelastase (MMP-12) drives inflammation and pathological angiogenesis in retinal diseases. Inhibiting MMP-12 reduces vascular leakage and neovascularization but accelerates healthy revascularization.
Area of Science:
- Ophthalmology
- Immunology
- Vascular Biology
Background:
- Pathological angiogenesis causes vision loss in retinal diseases.
- Macrophage metalloelastase (MMP-12) is implicated in inflammation and angiogenesis.
Purpose of the Study:
- To investigate MMP-12's role in oxygen-induced retinopathy (OIR).
- To evaluate MMP-12 inhibition for treating pathological retinal neovascularization.
Main Methods:
- Utilized MMP-12 knockout (KO) mice and a pharmacological inhibitor (MMP408) in an OIR model.
- Assessed retinal vascular leakage, macrophage infiltration, inflammatory markers, and neovascularization.
Main Results:
- MMP-12 was upregulated in OIR, correlating with macrophage infiltration and inflammation.
- MMP-12 KO mice showed reduced vascular leakage, inflammation, and pathological neovascularization.
- MMP-12 deficiency impaired macrophage migration but accelerated healthy retinal revascularization.
Conclusions:
- MMP-12 is a key regulator of macrophage infiltration and inflammation in OIR.
- Targeting MMP-12 may treat pathological angiogenesis but could impact beneficial revascularization.
