Abstract
Increasing evidence suggests that trabecular meshwork (TM) cells participate in the regulation of intraocular pressure by controlling the rate of filtration of the aqueous humor. Ionic conductances that regulate cell volume and shape have been suggested to play an important role in TM cell volume regulation. Here, we compared ionic currents from TM cells derived from a normal subject (CTM) and from an individual affected by glaucoma (GTM). We found that while the ionic current types were similar, the current amplitudes and percentage of cells endowed with specific current at baseline were different in the two cell lines. Thus, we found that the majority of CTM cells were endowed with a swelling-activated Cl− current at baseline, whereas in the majority of GTM cells this current was not active at baseline and became activated only after perfusion with a hypotonic solution. An inward rectifier K+ current was also more prevalent in CTM than in GTM cells. Our work suggests that disregulation of one or more of these ionic currents may be at the basis of TM cell participation in the development of glaucoma.
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References
Bond TD, Ambikapathy S, Mohammad S, Valverde MA (1998) Osmosensitive C1-currents and their relevance to regulatory volume decrease in human intestinal T84 cells: outwardly vs. inwardly rectifying currents. J Physiol 511(pt 1):45–54
Cala PM (1980) Volume regulation by Amphiuma red blood cells. The membrane potential and its implications regarding the nature of the ion-flux pathways. J Gen Physiol 76:683–708
Comes N, Abad E, Morales M, Borras T, Gual A, Gasull X (2006) Identification and functional characterization of ClC-2 chloride channels in trabecular meshwork cells. Exp Eye Res 83:877–889
Dismuke WM, Ellis DZ (2009) Activation of the BK(Ca) channel increases outflow facility and decreases trabecular meshwork cell volume. J Ocul Pharmacol Ther 25:309–314
Ellis DZ (2011) Guanylate cyclase activators, cell volume changes and IOP reduction. Cell Physiol Biochem 28:1145–1154
Gasull X, Ferrer E, Llobet A, Castellano A, Nicolas JM, Pales J, Gual A (2003) Cell membrane stretch modulates the high-conductance Ca2+-activated K+ channel in bovine trabecular meshwork cells. Invest Ophthalmol Vis Sci 44:706–714
Goel M, Sienkiewicz AE, Picciani R, Wang J, Lee RK, Bhattacharya SK (2012) Cochlin, intraocular pressure regulation and mechanosensing. PLoS ONE 7:e34309
Kaufman PL (2008) Enhancing trabecular outflow by disrupting the actin cytoskeleton, increasing uveoscleral outflow with prostaglandins, and understanding the pathophysiology of presbyopia interrogating Mother Nature: asking why, asking how, recognizing the signs, following the trail. Exp Eye Res 86:3–17
Llobet A, Gasull X, Pales J, Marti E, Gual A (2001) Identification of Kir2.1 channel activity in cultured trabecular meshwork cells. Invest Ophthalmol Vis Sci 42:2371–2379
Mitchell CH, Fleischhauer JC, Stamer WD, Peterson-Yantorno K, Civan MM (2002) Human trabecular meshwork cell volume regulation. Am J Physiol Cell Physiol 283:C315–C326
Morrison JC, Acott TS (2003) Anatomy and physiology of aqueous humor outflow. In: Morrison JC, Pollack IP (eds) Glaucoma science and practice. Thieme, New York, pp 34–41
Nilius B, Prenen J, Voets T, Eggermont J, Droogmans G (1998) Activation of volume-regulated chloride currents by reduction of intracellular ionic strength in bovine endothelial cells. J Physiol 506(pt 2):353–361
Sears R, Nuckolls F, Haura E, Taya Y, Tamai K, Nevins JR (2000) Multiple Ras-dependent phosphorylation pathways regulate Myc protein stability. Genes Dev 14:2501–2514
Soto D, Comes N, Ferrer E, Morales M, Escalada A, Pales J, Solsona C, Gual A, Gasull X (2004) Modulation of aqueous humor outflow by ionic mechanisms involved in trabecular meshwork cell volume regulation. Invest Ophthalmol Vis Sci 45:3650–3661
Stamer WD, Seftor RE, Snyder RW, Regan JW (1995) Cultured human trabecular meshwork cells express aquaporin-1 water channels. Curr Eye Res 14:1095–1100
Stumpff F, Wiederholt M (2000) Regulation of trabecular meshwork contractility. Ophthalmologica 214:33–53
Tamm ER (2009) The trabecular meshwork outflow pathways: structural and functional aspects. Exp Eye Res 88:648–655
Tripathi RC (1972) Aqueous outflow pathway in normal and glaucomatous eyes. Br J Ophthalmol 56:157–174
Voets T, Buyse G, Tytgat J, Droogmans G, Eggermont J, Nilius B (1996) The chloride current induced by expression of the protein pICln in Xenopus oocytes differs from the endogenous volume-sensitive chloride current. J Physiol 495(pt 2):441–447
Volk AP, Heise CK, Hougen JL, Artman CM, Volk KA, Wessels D, Soll DR, Nauseef WM, Lamb FS, Moreland JG (2008) ClC-3 and ICls well are required for normal neutrophil chemotaxis and shape change. J Biol Chem 283:34315–34326
Yeh E, Cunningham M, Arnold H, Chasse D, Monteith T, Ivaldi G, Hahn WC, Stukenberg PT, Shenolikar S, Uchida T, Counter CM, Nevins JR, Means AR, Sears R (2004) A signalling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells. Nat Cell Biol 6:308–318
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This work was supported by American Cancer Society (RGS-09-043-01-DDC) and NIH (RO1NS070969) Grants to L. B. and by Grant EY016112 and an RPB career award to S. K. B.
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Grant, J., Tran, V., Bhattacharya, S.K. et al. Ionic Currents of Human Trabecular Meshwork Cells from Control and Glaucoma Subjects. J Membrane Biol 246, 167–175 (2013). https://doi.org/10.1007/s00232-012-9517-4
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DOI: https://doi.org/10.1007/s00232-012-9517-4