Lens cells utilize Na, K-ATPase to preserve stable cytoplasmic composition and thus transparency. In order to overcome the difficulty of ion regulation in such a large mass of tightly packed cells, the lens is specialized such that epithelial cells, particularly at the lens equator, maintain a high activity of Na, K-ATPase while fiber cells have low Na, K-ATPase activity. This unequal distribution of Na, K-ATPase activity is important because it provides the driving force for circulating ionic currents that flow outward at the posterior pole, inward at the anterior pole. However there is a gap in our knowledge of how the unequal spatial localization of Na, K-ATPase activity is established because all lens cells, epithelium and fibers, have a similar abundance of Na, K-ATPase protein. The level of Na, K-ATPase protein expression in lens cells does not tally with Na, K-ATPase activity. Other factors seem to be involved. Here we plan to study how the epithelial cells achieve and maintain high Na, K-ATPase activity. Studies will be conducted to examine the link between activity of Na, K-ATPase and the ability of lens epithelial cells to synthesize new Na, K-ATPase protein (Aim I); determine whether oxidative posttranslational modification of Na, K-ATPase protein contributes to reduction of Na, K-ATPase activity (Aim II); and to determine whether tyrosine phosphorylation of the a subunit can bring about changes in Na, K-ATPase activity (Aim III). Results from these studies will give us a better understanding of lens ion regulation and lens cell specializations that underpin long term maintenance of lens transparency.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY009532-10
Application #
6477785
Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Liberman, Ellen S
Project Start
1993-01-01
Project End
2007-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
10
Fiscal Year
2002
Total Cost
$250,250
Indirect Cost
Name
University of Louisville
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
City
Louisville
State
KY
Country
United States
Zip Code
40292
Mandal, Amritlal; Shahidullah, Mohammad; Delamere, Nicholas A (2018) TRPV1-dependent ERK1/2 activation in porcine lens epithelium. Exp Eye Res 172:128-136
Delamere, Nicholas A; Mandal, Amritlal; Shahidullah, Mohammad (2016) The Significance of TRPV4 Channels and Hemichannels in the Lens and Ciliary Epithelium. J Ocul Pharmacol Ther 32:504-508
Gao, Junyuan; Sun, Xiurong; White, Thomas W et al. (2015) Feedback Regulation of Intracellular Hydrostatic Pressure in Surface Cells of the Lens. Biophys J 109:1830-9
Shahidullah, M; Mandal, A; Delamere, N A (2015) Damage to lens fiber cells causes TRPV4-dependent Src family kinase activation in the epithelium. Exp Eye Res 140:85-93
Mandal, Amritlal; Shahidullah, Mohammad; Delamere, Nicholas A (2015) Calcium entry via connexin hemichannels in lens epithelium. Exp Eye Res 132:52-8
Beckel, Jonathan M; Argall, Arthur J; Lim, Jason C et al. (2014) Mechanosensitive release of adenosine 5'-triphosphate through pannexin channels and mechanosensitive upregulation of pannexin channels in optic nerve head astrocytes: a mechanism for purinergic involvement in chronic strain. Glia 62:1486-501
Sanderson, Julie; Dartt, Darlene A; Trinkaus-Randall, Vickery et al. (2014) Purines in the eye: recent evidence for the physiological and pathological role of purines in the RPE, retinal neurons, astrocytes, Müller cells, lens, trabecular meshwork, cornea and lacrimal gland. Exp Eye Res 127:270-9
Shahidullah, Mohammad; Mandal, Amritlal; Delamere, Nicholas A (2012) TRPV4 in porcine lens epithelium regulates hemichannel-mediated ATP release and Na-K-ATPase activity. Am J Physiol Cell Physiol 302:C1751-61
Shahidullah, M; Mandal, A; Beimgraben, C et al. (2012) Hyposmotic stress causes ATP release and stimulates Na,K-ATPase activity in porcine lens. J Cell Physiol 227:1428-37
Mandal, A; Shahidullah, M; Beimgraben, C et al. (2011) The effect of endothelin-1 on Src-family tyrosine kinases and Na,K-ATPase activity in porcine lens epithelium. J Cell Physiol 226:2555-61

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