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Increased resistance to chronic oxidative stress with differentiation in ARPE-19 cells correlated with higher steady state levels of Hsp27 and Hsp70. Oxidative stress disrupted RPE cell junction and barrier integrity, which may contribute to the pathogenesis of diseases related to RPE through disruption of the blood-retinal barrier.

Matrix metalloproteinases (MMPs) and their inhibitors are believed to have a significant role in a number of vitreoretinal diseases, from proliferative vitreoretinopathy to age related macular degeneration. The aim of this review is to summarise the current knowledge of their involvement in these diseases and to postulate potential therapeutic strategies.MMPs are a tightly regulated family of zinc dependent endopeptidases that are capable of degrading all components of the extracellular matrix (ECM) and basement membranes.1 The ECM is a complex structure that influences the behaviour of its resident cells, and those in the process of migration, by providing specific contextual information. Enzymes that modify the ECM thus have the potential to aVect basic cell biology in many physiological and pathological processes.2 Remodelling of the ECM must occur with spatial and temporal precision for normal development, morphogenesis, homeostasis, and tissue repair. As matrix degradation is a prerequisite for malignant invasion and metastasis, it is not surprising that MMP biology has attracted considerable interest, with clinical oncology trials under way in several organ systems.4-7 New proteolytic functions are also being defined for these enzymes. These include the degradation of non-matrix macromolecules such as myelin basic protein, inactivation of 1 antitrypsin, release of sequestered growth factors from ECM, and cleavage of bioactive molecules from the cell surface.

This study highlights the importance of information satisfaction for perceived QoL in individuals with cancer. It is clearly important to identify specific information requirements during the diagnosis and treatment process in order to provide information that is congruent with patients' needs.

Objectives: To determine the role of systemic complement activation in the pathogenesis of age-related macular degeneration and to examine whether serum C3a des Arg reflects systemic complement activation, independent of individual complement component levels.Methods: Plasma complement C3a des Arg levels and a single nucleotide polymorphism at position 402 of the complement factor H gene (CFH) were determined in 3 groups of subjects: 42 subjects with early age-related maculopathy, 42 subjects with neovascular (wet) agerelated macular degeneration, and a control group of 38 subjects with no clinical evidence of age-related changes at the macula. Results:The median (range) of plasma complement C3a des Arg levels in the age-related maculopathy and neovascular age-related macular degeneration groups were 52.6 (2.8-198.1) ng/mL and 60.9 (3.1-173.1) ng/mL, re-spectively. The levels were significantly raised compared with the control group (n=38), which had a median (range) plasma complement C3a des Arg level of 40.3 (6.1-81.7) ng/mL (analysis of variance, P=.02). The concentration of plasma C3a des Arg did not differ significantly between those with different CFH genotypes (P =.07). Conclusion:Systemic activation of the complement system may contribute to the pathogenesis of age-related macular degeneration independent of CFH polymorphism. Clinical Relevance:The results of this study may be relevant to aiming new treatment strategies toward reducing systemic low-grade inflammation.