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Diabetic retinopathy induces an inflammatory response in the retina characterized by an increase in inflammatory cytokines and the activation of microglia. The degree of microglia activation may influence the extent of retina injury following retinal metabolic stress. We have previously shown that DR rats have elevated levels of advanced glycation end products (AGEs) in their blood. We have also suggested that AGEs might be involved in microglial activation and production of tumor necrosis factor alpha (TNF alpha). In this study, we attempted to confirm that AGEs induce the release of TNF alpha from rat retinal microglia using an in vitro microglia culture system, and concurrently to explore the mediating mechanisms. AGEs increased the protein secretion and mRNA expression of TNF alpha in cultured rat retinal microglia. These effects of AGEs were primarily mediated by reactive oxygen species (ROS). Furthermore, the inhibitors for mitogen-activated protein kinases (MAPK; p38, JNK and ERK 1/2) and nuclear factor-kB (NF-kB) could significantly decrease AGEs-induced TNF alpha release. AGEs-activated microglia showed an increase of NF-kB p65 nuclear translocation. These observations indicated that pathophysiological levels of AGEs may alter rat retinal microglia function by up-regulating TNF alpha expression and release via enhanced formation of intracellular ROS. AGEs-induced ROS subsequently activates MAPK (p38, JNK and ERK1/2) and NF-kB.

Diabetic retinopathy involves an inflammatory response in the retina characterized by an increase in inflammatory cytokines and activation of microglia. The degree of microglia activation may influence the extent of retina injury following an inflammatory stimulus. Cytokines, released by activated microglia, regulate the influx of inflammatory cells to the damaged area. Thus, therapeutic strategy to reduce cytokine expression in microglia would be neuroprotective. Sinomenine, an alkaloid isolated from the stem and root of Sinomenium acutum , has long been recognized as an anti-inflammatory drug for rheumatoid arthritis and also inhibits macrophage activation. In this study, we activated retinal microglia in culture with advanced glycation end products (AGEs) treatment and attempted to determine whether sinomenine could reduce the production of cytokines from the activated microglia at both gene and protein levels. Changes in inflammatory cytokines, TNF alpha, IL-1 beta and IL-6, were measured by semi-quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA) both in the presence and absence of AGEs. The effect of sinomenine on levels of reactive oxygen species (ROS) and the nuclear translocation of NF-kB p65 were studied with a laser confocal scanning microscope. AGEs treatment induced a significant release of TNF alpha, IL-1beta, and IL-6 from retinal microglia. Sinomenine could inhibit release of these cytokines. Sinomenine attenuated ROS production in a dose-dependent fashion and reduced the nuclear translocation of NF-kB p65 in AGEs-activated retinal microglia in culture.

Retinal neurodegenerative disease involves an inflammatory response in the retina characterized by an increase in inflammatory cytokines and activation of microglia. The degree of microglia activation may influence the extent of retinal injury following an inflammatory stimulus. Cytokines released by activated microglia regulate the influx of inflammatory cells to the damaged area. Thus, a therapeutic strategy to reduce cytokine expression in microglia would be neuroprotective. Minocycline, a semisynthetic tetracycline derivative, is known to protect rodent brain from ischemia and to inhibit microglial activation. In this study, we activated retinal microglia in culture with lipopolysaccharide (LPS) and attempted to determine whether minocycline could reduce the production of cytokines from activated microglia at both gene and protein levels. Changes in inflammatory cytokines, TNF-alpha and IL-1beta, were measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) in the presence or absence of LPS. We also measured the levels of nitric oxide (NO) by the nitrate reductase method under similar conditions. LPS treatment induced a significant upregulation of the mRNA and release of TNF-alpha, IL-1beta, and NO from retinal microglia. Minocycline inhibited these releases. Thus, minocycline might exert its antiinflammatory effect on microglia by inhibiting the expression and release of TNF-alpha, IL-1beta, and NO.

To evaluate the results of excimer retreatment for undercorrection or regression after laser in situ keratomileusis (LASIK).Eight-eight eyes received retreatment for undercorrection or regression after first LASIK (FLASIK) in 2 149 eyes in our photorefractive keratotectomy (PRK)/LASIK center from March, 1996 to July, 1999. They were divided into 2 groups according to their degrees of pre-FLASIK myopia spherical equivalents. Group I was/= 10.00 diopters (D) (41 eyes); group II was10.00 D (47 eyes). We analyzed the factors of FLASIK which led to the re-LASIK (RLASIK), and observed the mean spherical equivalents (MSE), the ratio within +/- 1.00 D of emmetropia, the uncorrected visual acuity (UCVA), the best corrected visual acuity (BCVA) and the complication after RLASIK for at least 1 year follow-up study.The retreatment ratio was 4.1% among the 2 149 eyes. In group II, the ratio was 2.3 times that of the group I. In the comparison with other eyes, the eyes received RLAISK had no difference in sex, laterality and age (P0.05). Over 50.0% had pre-FLASIK diopters/= 10.00 D, and 73.9% had astigmatism correction in FLASIK. After RLASIK, no undercorrection or regression occurred in group I, but there was undercorrection in group II. The ratio within +/- 1.00 D of emmetropia after 1 year was 68.3% in group I and 51.1% in group II. The UCVA above 0.5 was over 90.0% in all eyes. Eight eyes (9.0%) lost two or more lines of BCVA. The serious complication after RLASIK was keratoconus of 3 eyes in group II.The risk factors which lead to retreatment after FLASIK are high myopia with astigmatism before FLKSIK and the reaction to the operation. In this study, RLKSIK is safe, effective, predictable and accurate for/= -10.00 D correction in FLASIK. But, to prevent the occurrence of serious complication such as keratoconus, it is better not to perform RLASIK for-10.00 D in FLASIK.