interleukin-8 and Exfoliation-Syndrome

Exfoliation syndrome (XFS) produces deleterious ocular aging and has protean systemic manifestations. Local ocular production of TGFβ1 is of central importance in XFS. TGFβ1 appears to induce the expression of LOXL1 and the production of other extracellular matrix components which are known to be present in exfoliation material. Furthermore, results from several studies find that the aqueous humor of exfoliation glaucoma patients exhibits a decreased antioxidant defense and increased oxidative stress systems. Finally, studies show that the levels of interleukin-6 and interleukin-8 in the aqueous humor of XFS patients were 3-fold higher than in controls. Overall TGFβ1, as well as a prooxidative and proinflammatory environment seems to play an important role in XFS.

Topics: Amino Acid Oxidoreductases; Aqueous Humor; Exfoliation Syndrome; Extracellular Matrix; Glaucoma, Open-Angle; Humans; Inflammation; Interleukin-6; Interleukin-8; Intraocular Pressure; Oxidative Stress; Transforming Growth Factor beta1

Pseudoexfoliation (PEX) syndrome, which is an age-related, generalized elastotic matrix process, currently represents the most common identifiable risk factor for open-angle glaucoma. Dysregulated expression of proinflammatory cytokines has been implicated in the initiation of various fibrotic disorders and in the pathophysiology of glaucoma. Here we investigated the presence, expression, regulation, and functional significance of proinflammatory cytokines in eyes with early and late stages of PEX syndrome/glaucoma in comparison with normal and glaucomatous control eyes using multiplex bead analysis, immunoassays, real-time PCR, Western blotting, immunohistochemistry, and cell culture models. Early stages of PEX syndrome were characterized by approximately threefold (P < 0.005) elevated interleukin (IL)-6 and IL-8 levels in the aqueous humor and a concomitant approximately twofold (P < 0.001) increase in mRNA expression levels in anterior segment tissues as compared with controls. In contrast, late stages of PEX syndrome/glaucoma did not differ significantly from controls. IL-6, IL-6 receptor, and phospho-signal transducer and activator of transcription 3 could be mainly localized to walls of iris vessels and to the nonpigmented epithelium of ciliary processes. IL-6 and IL-8 were significantly up-regulated by ciliary epithelial cells in response to hypoxia or oxidative stress in vitro, whereas IL-6, but not IL-8, induced the expression of transforming growth factor-beta1 and elastic fiber proteins. These findings support a role for a stress-induced, spatially, and temporally restricted subclinical inflammation in the onset of the fibrotic matrix process characteristic of PEX syndrome/glaucoma.

Topics: Adult; Aged; Aged, 80 and over; Animals; Aqueous Humor; Cell Line; Cytokines; Exfoliation Syndrome; Extracellular Matrix; Eye; Female; Glaucoma, Open-Angle; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Molecular Sequence Data