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Macrophage-Like Cell Density and Distribution in Relation to Vascular Leakage in Diabetes
Ece Ozdemir Zeydanli1,2, Jay B Bisen1, Curtis J Heisel1
1Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Purpose:
To investigate the relationship between macrophage-like cell (MLC) density and vascular leakage in the macula, an indicator of blood-retinal barrier (BRB) breakdown, in diabetic retinopathy (DR), and to understand whether MLCs cluster within areas of vascular leakage.
Design:
Cross-sectional imaging analysis.
Subjects:
A total of 161 eyes from 152 diabetic participants with various stages of DR.
Methods:
Fluorescein angiography (FA) was used to delineate and quantify macular leakage and OCT angiography was used to visualize MLCs using an averaged 3-μm OCT slab above the vitreoretinal interface. In a subgroup of 36 eyes, MLC density maps were overlaid onto FA images to assess the spatial distribution of MLCs relative to leakage zones and their perimeter.
Main Outcome Measures:
Correlation between MLC density and macular leakage, and the spatial distribution of MLCs in relation to leakage zones.
Results:
A nonlinear relationship was observed between MLC density and macular leakage, captured by a quadratic model (r2 = 0.246, P < 0.001). Macrophage-like cell density increased with leakage, peaking between 50% and 60%, but then declined in eyes with more extensive leakage (>60%). Macrophage-like cells were more likely to cluster near leakage boundaries (P < 0.01), without difference in MLC density inside- versus outside-leakage areas (P = 0.08).
Conclusions:
The nonlinear relationship between MLC density and macular leakage in DR, along with MLC accumulation around the borders of leakage, suggest a nuanced role for these cells in DR and BRB breakdown. These findings also suggest a complex interplay among different macrophage populations and may reflect changes in MLC function or migration to deeper retinal layers with advancing leakage.
Financial Disclosures:
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Insights
Macrophage-like cells (MLCs) show a complex, nonlinear relationship with macular leakage in diabetic retinopathy (DR). These cells cluster around leakage borders, suggesting a nuanced role in blood-retinal barrier breakdown.
Area of Science:
- Ophthalmology
- Immunology
- Diabetic Retinopathy Research
Background:
- Diabetic retinopathy (DR) is a leading cause of vision loss, characterized by blood-retinal barrier (BRB) breakdown and macular leakage.
- Macrophage-like cells (MLCs) are implicated in inflammatory processes and tissue remodeling within the retina.
Purpose of the Study:
- To investigate the relationship between MLC density and macular leakage in DR.
- To determine if MLCs accumulate within or around areas of vascular leakage.
Main Methods:
- Cross-sectional imaging analysis of 161 eyes from 152 diabetic participants.
- Fluorescein angiography (FA) for quantifying macular leakage.
- OCT angiography to visualize MLCs and assess their spatial distribution relative to leakage zones.
Main Results:
- A nonlinear, quadratic relationship was found between MLC density and macular leakage (r² = 0.246, P < 0.001).
- MLC density peaked with 50-60% leakage and declined in eyes with >60% leakage.
- MLCs preferentially clustered near leakage boundaries (P < 0.01).
Conclusions:
- MLC density exhibits a complex, nonlinear association with macular leakage in DR.
- MLC accumulation at leakage borders suggests a specific role in BRB breakdown.
- Findings indicate a nuanced role for MLCs and potential changes in their function or migration in advanced DR.
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