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W.–H. Wang, L.G. McNatt, I.–H. Pang, P.E. Hellberg, C.J. Millar, A.F. Clark; Increased Expression of Serum Amyloid A in Human Glaucoma and Effect on IOP . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1545.
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© ARVO (1962-2015); The Authors (2016-present)
To identify differentially expressed genes in glaucomatous trabecular meshwork (TM) cells and tissues and to determine the effects of one of these genes, serum amyloid A (SAA), on glaucoma pathogenesis.
Affymetrix array (U133A/B) and real time RT–PCR were used to identify genes differentially expressed in normal and glaucomatous human TM tissues and cells. ELISA was used to examine protein expression in TM tissues and cells as well as in human aqueous humor samples. Recombinant SAA was added to perfusion cultured human anterior segments to determine effects on aqueous outflow facility. Intravitreal injection of Ad5.SAA2 in mouse eyes was used to study effects of upregulated SAA2 expression on IOP.
Expression of the SAA1 and SAA2 mRNA was increased in glaucomatous TM tissues (5.3–fold, p<0.05, n=12 glaucoma vs. 11 normal) and cultured TM cells derived from glaucomatous donors (5.4–fold, n=14 glaucoma vs.11 normal). SAA protein was significantly elevated (3–fold, p<0.05) in glaucomatous TM tissues (11.2 ± 3.0 µg/mg protein, n = 7) compared to normal TM tissues (3.8 ± 1.5 µg/mg protein, n = 6). SAA protein was also significantly elevated (3.1–fold, p<0.005) in human glaucomatous aqueous humor (11.4 ± 2.4 ng/ml, n = 22) compared to normal (3.7 ± 1.4 ng/ml, n = 16). The addition of recombinant SAA (1µg/ml) to perfusion cultured human anterior segments caused a significant decrease in outflow facility (∼ 40%, n = 5, p<0.05). Intravitreal injection of Ad5.SAA2 (7 x 106 pfu/eye) in mice significantly increased IOP (49% or 5.8 mmHg, n = 6, p<0.05).
SAA is an acute phase apolipoprotein that regulates cytokine expression and causes amyloid deposition. It has been used as a marker for inflammatory diseases. This study documents novel aspects of SAA relevant to the pathogenesis of glaucoma. Over–expression of SAA occurs in glaucomatous TM cells, TM tissue, and aqueous humor. SAA caused significantly decreased aqueous outflow in perfused human anterior segments and increased IOP in the mouse. Therefore, increased expression of SAA in glaucomatous TM and aqueous humor may contribute to the pathogenic changes in the TM, resulting in ocular hypertension.
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