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Glaucoma: Won-Kyu Ju, Quan Liu, Keun-Young Kim, Jonathan G. Crowston, James D. Lindsey, Neeraj Agarwal, Mark H. Ellisman, Guy A. Perkins, and Robert N. Weinreb Elevated Hydrostatic Pressure Triggers Mitochondrial Fission and Decreases Cellular ATP in Differentiated RGC-5 Cells Invest. Ophthalmol. Vis. Sci. 2007; 48: 2145-2151 [Abstract] [Full text] [PDF]

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In Vitro Hydrostatic Pressure Models of Glaucoma: The Importance of Henry's Law

Mark Johnson   (7 December 2007)

Author Response: In Vitro Hydrostatic Pressure Models of Glaucoma: The Importance of Henry's Law

Won-Kyu Ju   (7 December 2007)

In Vitro Hydrostatic Pressure Models of Glaucoma: The Importance of Henry's Law 7 December 2007
Mark Johnson Send letter to journal: Re: In Vitro Hydrostatic Pressure Models of Glaucoma: The Importance of Henry's Law m-johnson2{at}northwestern.edu Mark Johnson	We read with interest the article by Ju et al. entitled "Elevated hydrostatic pressure triggers mitochondrial fission and decreases cellular ATP in differentiated RGC-5 cells."1 They found that small changes in hydrostatic pressure affected retinal ganglion cell function. They attributed these effects directly to the change in hydrostatic pressure rather than to secondary changes such as dissolved gas concentration in the culture medium. In support of this conclusion, they demonstrated that "hydrostatic pressure did not cause any difference in pH or the vital gases in cultures subjected to pressure, compared with control cultures suggesting that the pressure system did not significantly alter the gas relationships in the RGC-5 cultures." We find this surprising. Henry's law indicates that the amount of gas dissolved in a liquid is directly proportional to the partial pressure of that gas in equilibrium with the liquid. An increase in pressure of 30 mm Hg would be expected to increase the partial pressure of oxygen in the gas (and hence in the culture media) by approximately 4%. We wonder why the oxygen concentration in solution was not increased by the altered partial pressure of oxygen in the gas. We also wondered as to the relevance of hydrostatic pressure effects as they relate to glaucoma.2 The measured IOP determines the extent to which the pressure in the eye is greater than the ambient atmospheric pressure, and it is presumably an increase in this pressure difference than can damage retinal ganglion cells and cause glaucoma. If an increase in the ambient hydrostatic pressure per se was important, would not a much lower incidence of glaucoma be expected in cities like Denver where the ambient hydrostatic pressure is approximately 140 mm Hg less than at sea level? Mark Johnson1 C. Ross Ethier2 David L. Epstein3 1Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 2Institute of Biomaterials and Biomedical Engineering, University of Toronto, Ontario, Canada 3Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina References 1. Ju W-K, Liu Q, Kim K-Y, et al. Elevated hydrostatic pressure triggers mitochondrial fission and decreases cellular ATP in differentiated RGC-5 cells. Invest Ophthalmol Vis Sci. 2007;48:2145-2151. 2. Ethier CR, Johnson M. Hydrostatic pressure is not a surrogate for IOP in glaucoma (E-letter). Invest Ophthalmol Vis Sci. Available at http://www.iovs.org/cgi/eletters/46/8/2829#304. Published February 21, 2006.
Author Response: In Vitro Hydrostatic Pressure Models of Glaucoma: The Importance of Henry's Law 7 December 2007
Won-Kyu Ju Send letter to journal: Re: Author Response: In Vitro Hydrostatic Pressure Models of Glaucoma: The Importance of Henry's Law danielju{at}glaucoma.ucsd.edu Won-Kyu Ju	We thank Drs. Johnson, Ethier and Epstein for their interest in our article.1 The main purpose of our study was to determine whether elevated hydrostatic pressure induces mitochondrial fission and dysfunction in cultured retinal ganglion cells. Some interesting points are raised. We agree that an increase in pressure of 30 mm Hg would be expected to increase the partial pressure of oxygen in the culture media by approximately 4%. These differences may reflect the accuracy limitation of the blood-gas analyzer. The letter also raises an interesting point about the relevance of between hydrostatic pressure effect and glaucoma.2 We agree that the difference of pressure between the inside and the outside of the eye is likely to be important in glaucoma. Studies investigating the effect of altitude on glaucoma prevalence, in which age, genetic background, and glaucoma risk factors are considered are lacking. Our results support the need for such studies as well as further basic studies on the direct effects of pressure on retinal ganglion cell mitochondria. Won-Kyu Ju1 Jonathan G. Crowston2 James D. Lindsey1 Robert N. Weinreb1 1Hamilton Glaucoma Center, Department of Ophthalmology, University of California San Diego, La Jolla, California 2Glaucoma Unit, Department of Ophthalmology, University of Melbourne, East Melbourne, Australia References 1. Ju W-K, Liu Q, Kim K-Y, et al. Elevated hydrostatic pressure triggers mitochondrial fission and decreases cellular ATP in differentiated RGC-5 cells. Invest Ophthalmol Vis Sci. 2007;48:2145-2151. 2. Ethier CR, Johnson M. Hydrostatic pressure is not a surrogate for IOP in glaucoma (E-letter). Invest Ophthalmol Vis Sci. Available at http://www.iovs.org/cgi/eletters/46/8/2829#304. Published February 21, 2006.