Indiana University School of Optometry
Faculty Research: Joseph A. Bonanno, OD, PhD
Variability in Corneal Swelling and Oxygen Consumption

When the cornea is made hypoxic, for example by wearing a contact lens, glycolytic metabolism is stimulated and as a consequence lactate and proton production increases. In addition to a decrease in corneal pH from the proton production, the excess lactate in the cornea will act as an osmotic stimulus, drawing water into the cornea causing edema. Interestingly, in a group of normal human subjects (who were not wearing contact lenses), given the same hypoxic stimulus, there is a wide range of corneal swelling responses. We found that this variability could be partially explained by intersubject variability in acid production and the oxygen consumption rate of each subject's cornea (see publication #1).

A group of contact lens wearers also show variability in swelling and corneal metabolism. However, compared to the no lens wearers they showed less corneal edema, less acid production (i.e., lactate), but the same corneal oxygen consumption (see publication #2). We hypothesize that this "adaptation to hypoxia" probably results from alterations in mitochondrial function. Specifically, we will be testing the hypothesis that hypoxia adapted mitochondrial express less Uncoupling Protein-2 (UCP2). Better coupling of electron transport to ATP production makes the hypoxia adapted cells more efficient so they produce less lactate from glycolysis and therefore less corneal edema when wearing a contact lens.

We have also found that hypoxia adapted corneal cells grown in culture are protected from UV induced cell death. We are currently investigating the mechanisms for this protection and whether hypoxia preconditioning could be used to protect cells during photoablative corneal surgery.

Recent Publications on Corneal Metabolism

1. Tracy Nguyen, P. Sarita Soni, Edward Brizendine, Joseph A. Bonanno. "Variability in hypoxia-induced corneal swelling is associated with variability in corneal metabolism and endothelial function" Eye and Contact Lens, 29: 117-125, 2003.
2. Joseph A. Bonanno, Tracy Nguyen, Trina Biehl, Sarita Soni. "Can variability in corneal metabolism explain the variability in corneal swelling?" Eye and Contact Lens Research 29(1S): S7-9, 2003.
3. Joseph A. Bonanno, Thomas Stickel, Tracy Nguyen, Trina Biehl, Donna Carter, William J. Benjamin, P. Sarita Soni. "Direct Estimation of Human Corneal Oxygen Consumption by Non-Invasive Measurement of Tear Oxygen Tension While Wearing Hydrogel Contact Lenses." Invest. Ophthalmol. Vis. Sci. 43:371-376, 2002.
4. Harvitt DM and Bonanno JA. Oxygen consumption of the rabbit cornea. Invest Ophthalmol Vis Sci, 39(2): 444-448, 1998.
5. Harvitt DM and Bonanno, JA. pH dependence of corneal oxygen consumption. Invest Ophthalmol Vis Sci., 39: 2778-81, 1998.
6. Harvitt D and Bonanno, JA. Re-evaluation of the oxygen diffusion model for predicting minimum contact lens Dk/t values needed to avoid corneal anoxia. Optometry and Vision Science 76:712-719, 1999.

Lab Personnel

Colin Cheng	Miao Cui	Jinhua Li	Tracy Nguyen
Kah Tan	Qiang Xie	Dongmei Xing	Yan Zhang

	URL: http://www.opt.indiana.edu/people/faculty/bonanno/hypoxia.htm Revised: November 23, 2004
	IU Optometry home page: http://www.opt.indiana.edu/ Comments: Web Administrator Original page design and coding: Terri Greene Copyright © 2004, The Trustees of Indiana University