Molecular Mechanisms Underlying the Corneal Endothelial Pump

Overview

Journal Exp Eye Res

Specialty Ophthalmology

Date 2011 Jun 23

PMID 21693119

Citations 141

Authors

Joseph A Bonanno

Affiliations

Soon will be listed here.

Abstract

The corneal endothelium is responsible for maintaining the hydration of the cornea. This is through a "Pump-Leak" mechanism where the active transport properties of the endothelium represent the "Pump" and the stromal swelling pressure represents the "Leak". For the "Pump", Na(+), K(+) ATPase activity and the presence of HCO(3)(-), Cl(-), and carbonic anhydrase activity are required. Several basolateral (stromal side) anion transporters, apical (facing the aqueous humor) ion channels and water channels have been identified that could support a model for ion secretion as the basis for the endothelial pump, however evidence of sustained anion fluxes, osmotic gradients or the need for water channels is lacking. This has prompted consideration of other models, such as Electro-osmosis, and consideration of metabolite flux as components of the endothelial pump. Although the conditions under which the "Pump" is supported are known, a complete model of the endothelial "Pump" has yet to emerge.

Citing Articles

The Application of Terahertz Technology in Corneas and Corneal Diseases: A Systematic Review.

Chow B, Liu C, Yu M, Yu Lee I, Mehta J, Wu Q Bioengineering (Basel). 2025; 12(1).

PMID: 39851319 PMC: 11762122. DOI: 10.3390/bioengineering12010045.

ROCK Inhibitor Enhances Resilience Against Metabolic Stress Through Increasing Bioenergetic Capacity in Corneal Endothelial Cells.

Ho W, Chang J, Lei C, Chen T, Wang J, Chang S Invest Ophthalmol Vis Sci. 2025; 66(1):51.

PMID: 39847368 PMC: 11759620. DOI: 10.1167/iovs.66.1.51.

Correlation between preoperative aqueous cytokine levels and mid-term corneal endothelial cell loss following penetrating keratoplasty.

Matsumae H, Kataoka K, Yagi-Yaguchi Y, Higa K, Suzuki T, Kasamatsu H Eye (Lond). 2025; .

PMID: 39833574 DOI: 10.1038/s41433-025-03610-x.

Retrospective Clinical Outcomes of Keratoplasty Using Human Donor Corneas Preserved in Eusol-C Hypothermic Storage Medium.

Colabelli Gisoldi R, Pocobelli G, Rodella U, Giurgola L, Gatto C, Lodato G J Clin Med. 2025; 13(24.

PMID: 39768528 PMC: 11677598. DOI: 10.3390/jcm13247606.

Towards Clinical Application: Calcium Waves for In Vitro Qualitative Assessment of Propagated Primary Human Corneal Endothelial Cells.

Ng X, Peh G, Morales-Wong F, Gabriel R, Soong P, Lin K Cells. 2024; 13(23).

PMID: 39682760 PMC: 11640329. DOI: 10.3390/cells13232012.

References

Baum J, LEVENE R . Corneal thickness after topical corticosteroid therapy. Arch Ophthalmol. 1968; 79(4):366-9. DOI: 10.1001/archopht.1968.03850040368003. View

Loo D, Zeuthen T, Chandy G, Wright E . Cotransport of water by the Na+/glucose cotransporter. Proc Natl Acad Sci U S A. 1996; 93(23):13367-70. PMC: 24099. DOI: 10.1073/pnas.93.23.13367. View

Chhabra M, Prausnitz J, Radke C . Modeling corneal metabolism and oxygen transport during contact lens wear. Optom Vis Sci. 2009; 86(5):454-66. DOI: 10.1097/OPX.0b013e31819f9e70. View

Ma T, Fukuda N, Song Y, Matthay M, Verkman A . Lung fluid transport in aquaporin-5 knockout mice. J Clin Invest. 2000; 105(1):93-100. PMC: 382590. DOI: 10.1172/JCI8258. View

Dikstein S, MAURICE D . The metabolic basis to the fluid pump in the cornea. J Physiol. 1972; 221(1):29-41. PMC: 1331317. DOI: 10.1113/jphysiol.1972.sp009736. View

Doughty M, Maurice D . Bicarbonate sensitivity of rabbit corneal endothelium fluid pump in vitro. Invest Ophthalmol Vis Sci. 1988; 29(2):216-23. View

Hatou S, Yamada M, Mochizuki H, Shiraishi A, Joko T, Nishida T . The effects of dexamethasone on the Na,K-ATPase activity and pump function of corneal endothelial cells. Curr Eye Res. 2009; 34(5):347-54. DOI: 10.1080/02713680902829624. View

Klyce S . Stromal lactate accumulation can account for corneal oedema osmotically following epithelial hypoxia in the rabbit. J Physiol. 1981; 321:49-64. PMC: 1249613. DOI: 10.1113/jphysiol.1981.sp013971. View

DIECKE F, Zhu Z, Kang F, Kuang K, Fischbarg J . Sodium, potassium, two chloride cotransport in corneal endothelium: characterization and possible role in volume regulation and fluid transport. Invest Ophthalmol Vis Sci. 1998; 39(1):104-10. View

10.

Xie Q, Zhang Y, Zhai C, Bonanno J . Calcium influx factor from cytochrome P-450 metabolism and secretion-like coupling mechanisms for capacitative calcium entry in corneal endothelial cells. J Biol Chem. 2002; 277(19):16559-66. DOI: 10.1074/jbc.M109518200. View

11.

Riley M . Glucose and oxygen utilization by the rabbit cornea. Exp Eye Res. 1969; 8(2):193-200. DOI: 10.1016/s0014-4835(69)80031-x. View

12.

Riley M, WINKLER B, Starnes C, Peters M . Fluid and ion transport in corneal endothelium: insensitivity to modulators of Na(+)-K(+)-2Cl- cotransport. Am J Physiol. 1997; 273(5):C1480-6. DOI: 10.1152/ajpcell.1997.273.5.C1480. View

13.

Zhang Y, Li J, Xie Q, Bonanno J . Molecular expression and functional involvement of the bovine calcium-activated chloride channel 1 (bCLCA1) in apical HCO3- permeability of bovine corneal endothelium. Exp Eye Res. 2006; 83(5):1215-24. PMC: 3108034. DOI: 10.1016/j.exer.2006.06.011. View

14.

Soltau J, Zhou L, McLaughlin B . Isolation of plasma membrane domains from bovine corneal endothelial cells. Exp Eye Res. 1993; 56(1):115-20. DOI: 10.1006/exer.1993.1016. View

15.

Srinivas S, Bonanno J, Hughes B . Assessment of swelling-activated Cl- channels using the halide-sensitive fluorescent indicator 6-methoxy-N-(3-sulfopropyl)quinolinium. Biophys J. 1998; 75(1):115-23. PMC: 1299684. DOI: 10.1016/S0006-3495(98)77499-5. View

16.

Hamann S, Kiilgaard J, La Cour M, Prause J, Zeuthen T . Cotransport of H+, lactate, and H2O in porcine retinal pigment epithelial cells. Exp Eye Res. 2003; 76(4):493-504. DOI: 10.1016/s0014-4835(02)00329-9. View

17.

Sun X, Bonanno J . Expression, localization, and functional evaluation of CFTR in bovine corneal endothelial cells. Am J Physiol Cell Physiol. 2002; 282(4):C673-83. PMC: 4100724. DOI: 10.1152/ajpcell.00384.2001. View

18.

Mirshahi M, Nicolas C, Mirshahi S, Golestaneh N, DHermies F, Agarwal M . Immunochemical analysis of the sodium channel in rodent and human eye. Exp Eye Res. 1999; 69(1):21-32. DOI: 10.1006/exer.1999.0675. View

19.

Sanchez J, Li Y, Rubashkin A, Iserovich P, Wen Q, Ruberti J . Evidence for a central role for electro-osmosis in fluid transport by corneal endothelium. J Membr Biol. 2002; 187(1):37-50. DOI: 10.1007/s00232-001-0151-9. View

20.

Tan-Allen K, Sun X, Bonanno J . Characterization of adenosine receptors in bovine corneal endothelium. Exp Eye Res. 2005; 80(5):687-96. PMC: 4113554. DOI: 10.1016/j.exer.2004.12.002. View