Abstract
Purpose: :
Previous studies suggested that oxidative stress is an important contributor to the development of glaucoma. To further our understanding of how known glaucoma risk factors correlate with oxidant-antioxidant balance, we measured levels and distribution of oxygen (pO2) in patients undergoing intraocular surgery.
Methods: :
Consenting patients undergoing cataract and/or glaucoma surgery were included. An Oxylab pO2TM optical oxygen sensor (Oxford Optronix) was introduced via 30G corneal paracentesis. In all patients, pO2 was sampled in the anterior chamber (AC) angle, mid-AC, and near the central corneal endothelium. In pseudophakes or eyes undergoing lens extraction, the probe was also introduced into the posterior chamber (PC) and near the anterior lens surface. Aqueous humor from 36 subjects with the lowest or highest pO2 was analyzed by small-molecule "metabolomic" profiling (Metabolon, Durham, NC).
Results: :
106 patients participated. In the reference group (eyes undergoing primary surgery), African-American subjects (n=17) had significantly higher pO2 than Caucasians (n=53) beneath the central cornea, in the mid-AC, near the lens, and in the PC (p=0.0061, 0.0173, 0.0034, 0.0166, respectively). pO2 was also higher in the AC angle of African-American subjects, but this difference was only marginally significant. Metabolomic analysis of aqueous humor revealed statistically significant elevation of several acyl-carnitines in patients with lower oxygen levels in the aqueous humor, compared to those patients with higher levels of pO2.
Conclusions: :
We found a statistically significant direct correlation of self-reported African-American race with anterior segment oxygen levels. African heritage is an important risk factor for development of open angle glaucoma and has been associated with differences in systemic oxidative metabolism, specifically mitochondrial oxidative capacity. The genetic and biochemical basis for these racial differences has yet to be defined. We are not aware of prior studies evaluating ocular metabolic variations in different races. Mitochondrial activity is reflected by acyl-carnitine transport. Lower levels of acyl-carnitines and elevated oxygen in the aqueous suggest that racial differences in mitochondrial activity underlie these differences in ocular metabolism. Further study of mitochondrial oxidative metabolism may provide insight about risk factors for glaucoma.
Keywords: aqueous • oxidation/oxidative or free radical damage • clinical (human) or epidemiologic studies: risk factor assessment