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Anil Kumar, Lian Zhao, Robert N Fariss, Wai T Wong; Interaction between resident macrophages and perivascular mural cells of the choroid: Relevance to pathological choroidal changes in retinal disease. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4458.
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Pathological choroidal vascular changes have been associated with retinal diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR), including changes in perivascular mural cells (PMCs) (i.e. pericytes and smooth muscle cells). We investigated how resident macrophages in the choroid may contribute to changes in PMC structure and function.
αSMA-GFP transgenic mice containing GFP+ PMCs were used to visualize vascular interactions with resident choroidal macrophages which were labeled with antibodies to MHC-II.. The effects of polarized human THP1 macrophages on human retinal pericyte cells (HRPC) were assessed in vitro using a TUNEL assay (apoptosis), a MTT assay (cell survival), and a BrdU assay (proliferation).
Perivascular ramified MHC-II macrophages, resident throughout the adult mouse choroid, was observed to contact PMCs via branched and motile processes. At the level of choroidal arteries and arterioles, the termini of macrophage processes made multiple focal contacts on PMC somata and encircling processes. At the level of choriocapillaris, stellate-shaped macrophages closely fasciculated their processes with those of flattened pericytes located on the sclerad surface of the choriocapillaris. These intimate and extensive intercellular contacts indicated that macrophage-PMC interactions occur constitutively in the choroid and may regulate vascular structure and function. In in vitro experiments, conditioned media from M1- and M2-polarized THP1 macrophages, were capable of differentially affecting HRPC pericyte proliferation and survival. M2-conditioned media induced in pericytes (1) increased proliferation (2) increased survival, and (3) a transition to an elongated morphology, while M1-conditioned media conversely (1) decreased proliferation, (2) increased apoptosis, and (3) promoted a transition to a rounded morphology.
Macrophages resident in the healthy adult choroid demonstrate extensive physical interactions with PMCs, suggestive of ongoing signaling. Alterations in macrophage polarization in retinal and choroidal disease may influence pericyte density, survival and function and drive pathological vascular change in the choroid. Macrophage-PMC interactions may play a role in retinal disease pathogenesis and constitute potential targets for intervention.
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