期刊
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 62, 期 6, 页码 -出版社
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.62.6.3
关键词
TGF beta 2; ID proteins; intraocular pressure; trabecular meshwork; outflow facility
资金
- Sigma Xi [G20141015669897]
Elevated intraocular pressure (IOP) in primary open-angle glaucoma (POAG) is a major risk factor for irreversible vision loss. Over-expression of ID1 and ID3 can suppress TGF beta 2-induced ocular hypertension and decreased aqueous humor (AH) outflow facility. These proteins may be potential candidates for future IOP-lowering treatments in POAG.
PURPOSE. In POAG, elevated IOP remains the major risk factor in irreversible vision loss. Increased TGF beta 2 expression in POAG aqueous humor and in the trabecular meshwork (TM) amplifies extracellular matrix (ECM) deposition and reduces ECM turnover in the TM, leading to a decreased aqueous humor (AH) outflow facility and increased IOP. Inhibitor of DNA binding proteins (ID1 and ID3) inhibit TGF beta 2-induced fibronectin and PAI-1 production in TM cells. We examined the effects of ID1 and ID3 gene expression on TGF beta 2-induced ocular hypertension and decreased AH outflow facility in living mouse eyes. METHODS. IOP and AH outflow facility changes were determined using a mouse model of Ad5-hTGF beta 2(C226S/C288S)-induced ocular hypertension. The physiological function of ID1 and ID3 genes were evaluated using Ad5 viral vectors to enhance or knockdown ID1/ID3 gene expression in the TM of BALB/cJ mice. IOP was measured in conscious mice using a Tonolab impact tonometer. AH outflow facilities were determined by constant flow infusion in live mice. RESULTS. Over-expressing ID1 and ID3 significantly blocked TGF beta 2-induced ocular hypertension (P < 0.0001). Although AH outflow facility was significantly decreased in TGF beta 2-transduced eyes (P < 0.04), normal outflow facility was preserved in eyes injected concurrently with ID1 or ID3 along with TGF beta 2. Knockdown of ID1 or ID3 expression exacerbated TGF beta 2-induced ocular hypertension. CONCLUSIONS. Increased expression of ID1 and ID3 suppressed both TGF beta 2-elevated IOP and decreased AH outflow facility. ID1 and/or ID3 proteins thus may show promise as future candidates as IOP-lowering targets in POAG.
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