​​Aging-US: Retinal pigment epithelial cells – implication in subretinal immune privilege

09-08-2021

Aging-US published a Special Collection on Eye Disease which included "The expression of C1 inhibitor (C1INH) in macrophages is upregulated by retinal pigment epithelial cells – implication in subretinal immune privilege in the aging eye" which reported that this study aimed to understand how complement expression in macrophages is regulated by retinal pigment epithelium (RPE) RPE can modulate macrophage complement expression at the retina-choroidal interface even under aging or oxidative conditions.

During inflammation, they may promote the alternative pathway of complement activation through down-regulating CFH and CD59a and upregulating C3, CFB and C1INH. When BMDMs were treated with apoptotic RPE, the expression of C1qb, CFH, and CD 59a was reduced but increased in BMDM. TNF-α pre-treated RPE enhanced C1inH and CFB expression.

Dr. Heping Xu from The Queen’s University Belfast as well as The Central South University said, "The neuronal retina is segregated from the systemic immune system by the blood retina barriers (BRB) and is considered as an immune privileged tissue."

Dr. Heping Xu from The Queen’s University Belfast as well as The Central South University said, "The neuronal retina is segregated from the systemic immune system by the blood retina barriers (BRB) and is considered as an immune privileged tissue."

The immune suppressive microenvironment of the eye is critical for retinal immune privilege.

Despite the lack of systemic immune surveillance, the retina is well-protected by its own innate immune defence system, including innate immune cells and the complement system. During aging, the expression of complement proteins or fragments is increased in the retina, particularly at the retina-choroid interface. Subretinal macrophages in the healthy adult eyes (6 -12 months old) often have a small soma and long- fine-dendrites (Fig. 1A), whereas the cells in the aging eye (20 – 27 months) have a large cell body that often contains pigmented debris. This suggests that they are active phagocytizing debris released by stressed RPE cells.

Figure 6. The effects of RPE/choroid eye-cup on BMDM complement gene expression. Naïve BMDMs were cultured in RPE/choroid eye cup from 18 months old mice for 7h. Macrophages were then isolated and processed for real-time RT-PCR analysis of complement genes. Mean ± SEM, n =3; *, P< 0.05; **, P < 0.01 compared to naïve BMDM alone, Unpaired Student t test.

The Xu Research Team concluded in their Aging-US Research Output, "we show that RPE cells can modulate macrophage complement expression. Under normal aging conditions, RPE cells may convert macrophages into a phenotype that can suppress complement activation with enhanced phagocytosis. This immune regulatory function of RPE cells on macrophages may be lost under inflammatory conditions. Instead, inflammatory or apoptotic RPE cells promote macrophages to produce complement components necessary for the AP activation. RPE cells together with subretinal macrophages critically control complement activation at the retina-choroid interface in the ageing eye."

Full Text - https://www.aging-us.com/article/101474/text

Correspondence to: Heping Xu email: heping.xu@qub.ac.uk

Keywords: macrophages, retinal pigment epithelial cells, complement, aging, subretinal immune privilege

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Cancer and aging are two sides of age-related tumorigenesis.

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