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C. Hudson, S. T. Venkataraman, R. Rachmiel, Y. Buys, G. E. Trope, J. G. Flanagan; Plasma Levels of ET-1 and cGMP in Primary Open Angle Glaucoma (POAG) During Isoxic Hypercapnia. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4609.
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Previous work from our lab has shown a reduced magnitude of retinal vascular reactivity to isoxic hypercapnia in patients with untreated POAG (uPOAG) and progressive POAG (pPOAG) compared to controls. The primary aim of this study was to investigate the effect of hypercapnia on plasma Endothelin-1 (ET-1) and Cyclic Guanosine Monophosphate (cGMP) in uPOAG pre-treatment, uPOAG post-treatment, pPOAG and controls.
Nine patients with uPOAG (mean age 53 yrs, range 27-65), 12 patients with pPOAG (mean age 63yrs, range 51-75) and 16 controls (mean age 55yrs, range 44-56) were studied. Isoxic hypercapnia was achieved using a computer driven gas flow controller. Blood samples were collected at baseline and during isoxic hypercapnia. Patients with uPOAG were treated with Dorzolamide 2% for 2 weeks and plasma endothelial factors were reassessed. ET-1 and cGMP levels were analysed using human ET-1 immunoassays (R& D systems, MN, USA) and the cyclic GMP EIA kit (Cayman Chemical, MI, USA), respectively.
Baseline levels of ET-1 in uPOAG pre-treatment and uPOAG post-treatment were significantly lower than those of controls (p=0.007). The group mean change in ET-1 during hypercapnia showed a non-significant (ns) 9% decrease in uPOAG pre-treatment and a 2.8% (ns) increase in pPOAG and controls. The magnitude of change in cGMP from baseline to hypercapnia showed a 10% decrease in uPOAG pre-treatment and controls (ns) and a 1% decrease in pPOAG. In uPOAG post-treatment, a 2% decrease in ET-1 and a 3% increase in cGMP during hypercapnia were noted.
A decreased level of baseline plasma ET-1 was seen in uPOAG, pre- & post-treatment. These results may indicate an overall reduced level of endothelial vasoactive factors leading to vascular dysregulation in POAG. The value of cGMP as an indirect indicator of endothelial vasoactive factors is questionable.
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