Clinical research led by a Japanese team at Kyushu University Graduate School of Medical Sciences, Fukuoka, has suggested that overexpression of CD163 in the vitreous and fibrovascular membranes of patients with proliferative diabetic retinopathy (PDR) points to M2 macrophage involvement with progression of the disease. Levels of CD163 – a specific marker for M2 macrophage – appeared to be significantly higher in patients with PDR than in non-diabetic controls (p<0.0001). In addition, the average levels of soluble CD163 appeared significantly higher in eyes with fibrovascular membranes than in control eyes.
In PDR, fibrovascular membranes (FVMs), forming on the surface of the retina, are understood to represent a tissue remodelling process as the disease progresses. An increased expression of a matricelluar protein (periostin) in the FVMs and vitreous of patients with PDR suggest the protein may be involved in the development of such FVMs. As FVMs are characterised by the migration and proliferation of several cell types, including macrophage, it may be hypothesised that M2 macrophage are key contributors to FVM development, especially as they are known to be associated with tissue remodelling and fibrosis. To determine if the M2 macrophage specific marker (CD163) is involved in FVM formation in patients with PDR, levels of soluble (s)CD163, periostin and VEGF was measured in vitreous samples from 74 eyes of 62 patients with PDR, 20 eyes of 18 patients with proliferative vitreoretinopathy, and 56 eyes of 54 patients with non-diabetic ocular diseases (control group).
Results of the study indicated that concentrations of sCD163 and periostin in the vitreous were indeed higher in patients with PDR than in non-diabetic controls and there appeared to be a strong correlation between the vitreous concentrations of sCD163 and periostin. From the data collected the Japanese research group stated that, “together with the fact that M2 macrophages contribute to angiogenesis and fibrosis, these results indicate that among the subtypes of macrophages, the M2 phenotype is more likely to play a role in the formation of FVMs”. In addition, the research results suggested that the correlation “between vitreous levels of sCD163 and periostin in eyes with PDR, and the colocalisation of CD163 and periostin in eyes with FVMs supports the hypothesis that the recruited M2 macrophages in FVMs produce periostin leading to FVM formation”. Taken in conjunction with results from other studies, the research group were able to propose a possible mechanism for macrophage mediated FVM formation within which multiple targets may emerge for both disease monitoring and therapeutic intervention.