Featuring: Jeremy Lavine, MD, PhD
A recent Northwestern Medicine study led by Jeremy A. Lavine, MD, PhD, assistant professor of Ophthalmology and Medicine (Rheumatology), found that macrophage-like cell (MLC) density in the vitreoretinal interface is significantly increased in proliferative diabetic retinopathy (PDR) and was more pronounced in the perivascular region and on blood vessels compared to ischemic areas. The finding suggests a potential role of MLCs in retinal inflammation or damage.
Amani A. Fawzi, MD, the Cyrus Tang and Lee Jampol Professor of Ophthalmology, and medical students Jacob M. Wang, Janice X. Ong, and Peter L. Nesper, were co-authors of the study published in Investigative Ophthalmology & Visual Science.
Diabetes damages retinal capillaries, leading to capillary dropout and diabetic retinopathy (DR). In nonproliferative DR (NPDR), intraretinal angiogenesis causes microaneurysm formation, hemorrhaging, and edema, which can result in vision loss from macular edema. In proliferative DR (PDR), angiogenesis at the vitreoretinal interface can produce severe vision loss from vitreous hemorrhage and tractional retinal detachment. Macrophages are innate immune cells with diverse roles, including inflammatory, fibrotic, angiogenic, and reparative functions. In rodents, DR can be blunted by inhibiting macrophages and/or inflammation. Similarly, intravitreal steroids can reduce both macular edema and diabetic retinopathy severity in clinical trials. Recently, cells have been visualized at the vitreoretinal interface that display macrophage properties including macrophage cell surface markers, dendritiform morphology, and migratory behavior, which are termed macrophage-like cells (MLCs). Since DR is a disease where the vitreoretinal interface is anatomically important, macrophages are a crucial pathologic cell type, and both inflammation and angiogenesis are key mechanisms for DR pathogenesis, we hypothesized that MLCs would be increased during PDR. We performed macular optical coherence tomography angiography imaging to identify MLCs at the vitreoretinal interface in the following patient groups: healthy, diabetes without DR, NPDR, and PDR. We quantified MLC density and their location with respect to blood vessels. We found that MLC density was increased 3-4 fold in patients with PDR compared to all other groups. This novel finding implicates vitreoretinal MLCs in PDR pathology, where they may promote neovascularization and/or membrane formation. In addition, MLCs were more likely to be found on blood vessels or directly adjacent to blood vessels, suggesting that MLCs could be recruited from damaged blood vessels during PDR. In summary, MLCs are increased at the vitreoretinal interface during PDR and may represent an imaging biomarker for macrophage-driven inflammation.
Read the study.
Jeremy Lavine, MD, PhD, is an assistant professor of Ophthalmology and Medicine (Rheumatology) at Northwestern Medicine, and the lead author of this study.
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