| Background Proliferative vitreoretinopathy( PVR)can be viewed as a wound healing process in a specialised tissue. Cytokines secreted by retinal pigment epithelium (RPE) play a key role in cellular chemotaxis, migration, proliferation, collagen production, membrane formation and contraction. Clinical investigations have suggested that IL-1β, IL-6, IL-8 and INF-α are elevated in the vitreous of PVR at different stages. These cytokines are significantly related to the progression of PVR. Although refinements in surgical techniques and equipment have improved the success rate of surgery to repair retinal detarchment in recent years, recurrence due to reproliferation is not uncommon and remains the leading cause of failure of retinal reatarment surgery. Dexaniethasone and daunorubicin have been used to prevent the development of PVR effectively, but their intrinsic shortcomings make them not to be used widely. Researches are thus obligated to find safe and high-powered drugs to treat PVR. Interleukin-l receptor antigonist (IL-1Ra) is a nature occurring antigonist, which binds to IL-i receptors with similar affinities as do IL-α and IL- 1β without evoking intracellular signal transduction. Increase of IL-iRa can inhibit IL-i-mediated inflammatory. The proportion of IL-I and IL-1Ra may be important to keep balance of tissue microenvironment. 6 Purpose This study was to observe IL-1β IL-6.. IL-8 and TNF-ct production by RPE and its inhibition by IL-i Ra, IL-6 antisense oligoneucleotides(ASON), dexamethasone and daunorubicin, as well as to investigate the effects of IL-iRa and IL-6ASON on the prevention of PVR. Material and methods 1. In vitro study: (1) RPE were challenged by IL-Iα (1Ong/ml) andlor LPS(lO i-i glint). Condition medium(CM) and cell lysates were collected to detected IL-1β, IL-6, IL-8 and TNF-α protein production by enzyme-linked iinmunosorbent assy(ELISA). Iinmunohistochemistry (IHC) and in situ hibridization histochemistry(ISHH) were performed to detect protein and mRNA of IL-1β, IL-6, IL-8 and TNF-cL in cytoplasm. (2) IL-lRa(lOOnglml), IL-6ASON(2Onmol/ml), dexainethasone, daunorubicin and a combination of IL-iRa and dexamethasone were given to cultured RPE to observe the protein and mRNA expression of IL-6, IL-8 and TNF-a induced by IL-1α (10ng/ml). 2. In vivo study: RPE cells were injected into vitreous cavity of 24 rabbits (48eyes) to establish PVR model. IL-1 Ra( 1 OOng), IL-6ASON(2Onmol), dexamethasone, daunorubicin and a combination of IL-i Ra and dexamethasone were injected into vitreous cavity simultaneously. Prevalence of PVR and retinal detachment were observed by direct ophthalmoscopy, B-scan uttrasonography and pathology study. Results 1. Under basal condition, cultured RPE produced small quantities of IL-6, IL-8 and TNF-α which mostly were in cell lysates. IL-i 13 was not detected in CM. When challenging RPE with IL-1α or LPS, IL-6, IL-8 and TNF-α protein were present in conditioned medium and cell lysates, and maximum IL-6, IL-8 and TNF-α were measured 6h-8h postadministration. After that, the level of IL-6, IL-8 and TNF-α raised flatly and slowly. IL-6, IL-8 and TNF-α production increased significantly if RPE exposed to IL-1α plus LPS. Their quantities were 3500,3000 and 4510 7 pg.ml-1.10-6cells respectively when RPE coi...
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