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Editors Selection IGR 9-2

Basic research: Total serum amyloid A mRNA and TM

Comment by Stuart McKinnon on:

20999 Increased expression of serum amyloid a in glaucoma and its effect on intraocular pressure, Wang WH; McNatt LG; Pang IH et al., Investigative Ophthalmology and Visual Science, 2008; 49: 1916-1923

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Wang et al. (505) used Affymetrix gene chip arrays to assess dif-ferential gene expression in trabecular meshwork ™ taken from glaucomatous and normal post-mortem human eyes. Total serum amyloid A (SAA) mRNA was found to be significantly elevated by more than five-fold in glaucoma when compared to control TMs. SAA is an acute-phase apolipoprotein that regulates cytokine expression and regulates amyloid de-position, and has been localized in atherosclerotic plaques and in brains of Alzheimer's disease patients. The inducibly expressed SAA1 and SAA2 genes were upregulated by 2.9 and 5.5-fold, respectively, while the constitutively expressed SAA4 was not detected in either glaucoma or control TMs. In glaucomatous human TM cell cultures, upregula-tion of SAA gene expression was confirmed, as well as significant induction of interleukin-8 (IL-8). In perfused human anterior segment culture, SAA treatment not only induced IL-8 production, but also caused sustained IOP elevation. The authors offer two hypotheses for the molecular mechanism of SAA-induced ocular hypertension. Overexpression of SAA could lead to deposition of amyloid fibrils in the TM in a manner analogous to that seen in systemic amyloidosis, causing mechanical resistance to aqueous outflow. Alternatively, SAA could act at the cellular level, inducing signal transduction pathways and increasing production of cytokines such as tumor necrosis factor and interleukins. The authors found no immunohistologic evidence of amyloid deposition in affected eyes, and the upregulation of IL-8 and other genes in the affected TM samples indicates that induction of cellular signaling is the more probable scenario. SAA represents an intriguing and important new molecular target for pharmacological intervention in glaucoma.

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