Increased expression of serum amyloid A in glaucoma and its effect on intraocular pressure.
OBJECTIVE
To search for and validate potential molecular pathogenic mechanisms in the trabecular meshwork (TM) responsible for the elevated intraocular pressure (IOP) associated with glaucoma.


METHODS
Gene chip arrays were used to identify differential gene expression in glaucomatous TM tissues. Serum amyloid A (SAA) upregulation was subsequently confirmed with quantitative PCR (QPCR) and ELISA. The effect of SAA on gene expression of cultured human TM cells was tested with gene chip arrays and verified with ELISA, and its effect on IOP was evaluated in the human ocular perfusion organ culture.


RESULTS
Microarray analysis showed that the expression of SAA2 was increased in TM tissues from donors with glaucoma. This finding was subsequently confirmed by QPCR. The SAA mRNA levels were increased in glaucoma TM tissues by more than 5-fold (P < 0.05) and in cultured TM cells derived from donors with glaucoma by 25-fold (P < 0.05) compared with controls. SAA protein levels in the TM of glaucoma patients were also significantly (P < 0.05) elevated by 2.9-fold. Treatment of cultured human TM cells with recombinant SAA affected gene expression, including a 22-fold up-regulation of interleukin-8 (P < 0.001). SAA increased IOP by approximately 40% (P < 0.05) in the human ocular perfusion organ culture without any observable changes in the morphology of the tissues involved in aqueous outflow.


CONCLUSIONS
These findings indicate that SAA, which is an acute-phase apolipoprotein that plays important roles in infection, inflammation, and tissue repair, may contribute to the pathogenic changes to the TM in glaucoma.
Wang
Wan-Heng
WH
Alcon Research Ltd., 6201 South Freeway, Fort Worth, TX 76134, USA.
McNatt
Loretta G
LG
Pang
Iok-Hou
IH
Hellberg
Peggy E
PE
Fingert
John H
JH
McCartney
Mitchell D
MD
Clark
Abbot F
AF
D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D009924:Organ Culture Techniques; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000235:genetics* / Q000378:metabolism; D014129:Trabecular Meshwork / Q000378:metabolism*
D012333:RNA, Messenger; D000685:Serum Amyloid A Protein