Heping Xu
Department of Ophthalmology, University of Aberdeen
Purpose: Age-related macular degeneration (AMD) is the largest cause of untreatable blindness in the developed world. The pathogenesis of AMD is not fully understood. Recent evidence suggests that local inflammation in particular complement activation plays an important role. The aim of this study is therefore to understand how complement activation is regulated locally in retinal/choroidal interface.
Methods: The expression and distribution of complement factor H (CFH) and factor B (CFB) in mouse ocular tissues were investigated by immunohistochemistry of ocular cryosections and observed by confocal microscopy. Regulation of CFH and CFB gene expression by various cytokines or photoreceptor outer segment tips (POS) was investigated in vitro in cultured RPE cells. Changes in CFH or CFB gene expression after treatment were evaluated by RT-PCR. Result: In normal mouse eyes, CFH was detected in corneal epithelial cells, cilliary body, RPE cells, Bruch’s membrane and choroidal vessels. There is no significant change in either the expression level or the distribution pattern of CFH in ocular tissues of different ages of mice. CFB was exclusively detected in RPE cells in normal mice. The expression of CFB in RPE cell increases with age. In vitro in RPE cultures, the expression of CFH was negatively regulated by cytokine TNF-alpha and IL-6, whereas the expression of CFB was positively regulated by TNF-alpha and IFN-gamma. Incubation of RPE cells with normal non-oxidized POS did not alter the expression of CFH or CFB, whereas long-term incubation of RPE cells with oxidized POS significantly down-regulated CFH but not CFB expression. Conclusion: Complement regulatory factors CFH and CFB are produced locally in the retina/choroidal interface by RPE cells. The production of CFH and CFB in RPE cells is regulated differently by various cytokines and oxidized POS.
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