Faculty Directory

S.P. Srinivas

Associate Professor

S.P. Srinivas

OP 507

812-855-0132
srinivas@indiana.edu

Education
  • MS–1982 (I.I.T., Madras, India)
  • PhD–1987 (Drexel University)
Courses Taught

Systemic Pharmacology

Ocular Pharmacology

Biography

Dr. S.P. Srinivas received his Ph.D. in Chemical Engineering from Drexel University in 1987. He obtained his postdoctoral training at Stanford University in the area of ocular drug delivery, and then at University of California, Berkeley, in the area of corneal physiology.

Publications

D'hondt C, Ponsaerts R, Srinivas SP, Vereecke J, Himpens B. Reduced intercellular communication and altered morphology of bovine corneal endothelial cells with prolonged time in cell culture. Curr Eye Res. 2009 Jun;34(6):454-65.

Gupta C, Chauhan A, Mutharasan R, Srinivas SP, Measurement and Modeling of Diffusion Kinetics of a Lipophilic Molecule Across Rabbit Cornea. Pharm Res. 2010 Feb 25. [Epub ahead of print] PMID: 20182774.

Shivanna M, Jalimarada SS, Srinivas SP, Lovastatin inhibits the thrombin-induced loss of barrier integrity in bovine corneal endothelium., J Ocul Pharmacol Ther. 2010 Feb;26(1):1-10. PMID: 20148651.

R. Charanya, S.P. Srinivas, Actomyosin Contraction Regulates Formation and Disassembly of Adherens and Tight Junctions in the Corneal Endothelium, Invest Ophthalmol Vis Sci. 2009 Dec 17. [Epub ahead of print] PMID: 20019371.

Raf Ponsaerts, Catheleyne D'hondt, Priya Gomes, Geert Bultynck, SP Srinivas, Johan Vereecke, and Bernard Himpens, ATP release via connexin hemichannels and intercellular propagation of calcium waves in corneal endothelial cells (Review chapter; Extracellular ATP and adenosine as regulators of endothelial cell function: Implications for health and disease; Gerasimovskaya, Evgenia; Kaczmarek, Elzbieta (Eds.)) ISBN: 978-90-481-3434-2, Springer Verlag, January 3, 2010).

Srinivas SP, Dynamic Regulation of Barrier Integrity of the Corneal Endothelium. Optom Vis Sci. 2010 Feb 5. [Epub ahead of print] PMID: 20142793.

Shivanna M, Rajashekhar G, Srinivas SP. Barrier Dysfunction of the Corneal Endothelium in Response to TNF-{alpha}: Role of p38 MAP Kinase. Invest Ophthalmol Vis Sci. 2010 Mar;51(3):1575-82. Epub 2009 Sep 24.

Shivanna M, SP Srinivas. Microtubule stabilization opposes the (TNF-alpha)-induced loss in the barrier integrity of corneal endothelium. Exp Eye Res. 2009 Aug 18. [Epub ahead of print] PubMed PMID: 19695246.

Jalimarada SS, Shivanna M, Kini V, Mehta D, SP Srinivas. Microtubule disassembly breaks down the barrier integrity of corneal endothelium. Exp Eye Res. 2009 Sep;89(3):333-43. Epub 2009 Apr 2. PubMed PMID: 19345211; PubMed Central PMCID: PMC2745835.

Ponsaerts R, Dhondt C, Bultynck G, SP Srinivas, Vereecke JS, Himpens B. The Myosin II ATPase Inhibitor Blebbistatin Prevents Thrombin-induced Inhibition of Intercellular Calcium Wave Propagation in Corneal Endothelial Cells. Invest Ophthalmol Vis Sci. 2008 Jul 9.

Ramachandran C, Satpathy M, Mehta D, Srinivas SP. Forskolin induces Myosin light chain dephosphorylation in bovine trabecular meshwork cells. Curr Eye Res. 2008 Feb;33(2):169-76.

Guo Y, Ramachandran C, Satpathy M, Srinivas SP. Histamine-induced Myosin Light Chain Phosphorylation Breaks Down the Barrier Integrity of Cultured Corneal Epithelial Cells, Pharm Res. 2007 Oct;24(10):1824-33.

Guo Y, Satpathy M, Wilson G, Srinivas SP. Benzalkonium chloride induces dephosphorylation of Myosin light chain in cultured corneal epithelial cells. Invest Ophthalmol Vis Sci. 2007 May;48(5):2001-8.

D'hondt C, Srinivas SP, Vereecke J, Himpens B. Adenosine opposes thrombin-induced inhibition of intercellular calcium wave in corneal endothelial cells. Invest Ophthalmol Vis Sci. 2007 Apr;48(4):1518-27.

D'hondt C, Ponsaerts R, Srinivas SP, Vereecke J, Himpens B. Thrombin inhibits intercellular calcium wave propagation in corneal endothelial cells by modulation of hemichannels and gap junctions. Invest Ophthalmol Vis Sci. 2007 Jan;48(1):120-33.

Liu H, Begley CG, Chalmers R, Wilson G, Srinivas SP, Wilkinson JA. Temporal progression and spatial repeatability of tear breakup. Optom Vis Sci. 2006 Oct;83(10):723-30.

Gomes P, Srinivas SP, Vereecke J, Himpens B. Gap junctional intercellular communication in bovine corneal endothelial cells. Exp Eye Res. 2006 Nov;83(5):1225-37.

Srinivas SP, Satpathy M, Guo Y, Anandan V., Histamine-Induced Phosphorylation of the Regulatory Light Chain of Myosin II Disrupts the Barrier Integrity of Corneal Endothelial Cells. Invest Ophthalmol Vis Sci. 2006 Sep;47(9):4011-8.

Satpathy M, Gallagher P, Y.Lin, Srinivas SP. ATP opposes thrombin-induced MLC phosphorylation and breakdown of barrier integrity in cultured bovine corneal endothelial cells. Exp Eye Res. 2005 Aug;81(2):183-92.

Gomes P, Srinivas SP, Vereecke J, Himpens B. ATP Release through Connexin Hemichannels in Cultured Bovine Corneal Endothelial Cells. (In Press; Invest Ophthalmol Vis Sci., Jan 2005).

Gomes P, Srinivas SP, Vereecke J, Himpens B. ATP-Dependent Paracrine Intercellular Communication in Cultured Bovine Corneal Endothelial Cells. Invest Ophthalmol Vis Sci. 2005 Jan;46(1):104-13.

Satpathy, M., Gallagher, P., Lizotte-Waniewski, M. and Srinivas S.P. (2004) Thrombin-induced phosphorylation of the regulatory light chain of myosin II in cultured bovine corneal endothelial cells. Exp Eye Res.79: 477-486.

Srinivas, S.P., Satpathy, M., Gallagher, P., Lariviere, E., Van Driessche W. (2004) Adenosine induces MLC dephosphorylation in cultured bovine corneal endothelial cells. Exp Eye Res. 79(4): 543-551.

Srinivas, S.P., Maertens,C., Goon L.H.,Goon L., Satpathy, M., Yue, B.Y.J.T., Droogmans, G. and Nilius, B. (2004) Volume-regulated anion channels in cultured bovine trabecular meshwork cells. Exp Eye Res. Jan;78(1):15-26.

Srinivas S.P., Bonanno JA, Lariviere E, Jans D, Van Driessche W.(2003) Measurement of rapid changes in cell volume by forward light scattering. Pflugers Arch. Oct;447(1):97-108.

Srinivas S.P., Mutharasan R, Fleiszig S(2002) Shear-induced ATP release by cultured rabbit corneal epithelial cells. Adv Exp Med Biol. 506(Pt A):677-85

Jans D, Srinivas SP, Waelkens E, Segal A, Lariviere E, Simaels J, Van Driessche W. Hypotonic treatment evokes biphasic ATP release across the basolateral membrane of cultured renal epithelia (A6). J Physiol. 2002 Dec 1;545(Pt 2):543-55.

Srinivas SP, Ong A, Zhai CB, Bonanno JA. Inhibition of carbonic anhydrase activity in cultured bovine corneal endothelial cells by dorzolamide. Invest Ophthalmol Vis Sci. 2002 Oct;43(10):3273-8.

Srinivas SP, Ong A, Goon L, Goon L, Bonanno JA. Lysosomal Ca(2+) stores in bovine corneal endothelium. Invest Ophthalmol Vis Sci. 2002 Jul;43(7):2341-50.

Jans D, De Weer P, Srinivas SP, Lariviere E, Simaels J, Van Driessche W. Mg(2+)-sensitive non-capacitative basolateral Ca(2+) entry secondary to cell swelling in the polarized renal A6 epithelium. J Physiol. 2002 May 15;541(Pt 1):91-101.

S.P. Srinivas, R. Mutharasan, and S.M.J. Fleiszig, M, Shear stress induced ATP release in corneal epithelial cells in ÒLacrimal Gland, Tear Film & Dry Eye Syndromes 3: Basic Science and Clinical RelevanceÓ, Edited by D.A. Sullivan, 2002. [Not a peer-reviewed publication]

Mutharasan, R. and Srinivas, S.P. Transport of a Lipid-Soluble Drug Analog across the Cornea. Pharmaceutical and Biotechnology Topical Program Proceedings, Pages 56-62, Published by American Institute of Chemical Engineers, New York, NY. (2002).

Bonanno, J. A., Guan Yi, Xiao Jun Kang and S. P. Srinivas. Re-evaluation of Cl-/HCO3- exchange in cultured bovine corneal endothelial cells. Invest Ophthalmol Vis Sci. 1998 Dec;39(13):2713-22.

Srinivas, S.P., J.C.Yeh, and J.A. Bonanno. Ca2+ mobilization in bovine corneal endothelial cells by P2 purinergic receptors, Current Eye Research. 17:994-1004, 1998.

Srinivas, S.P., G.Yi, and J.A. Bonanno. Swelling Activated Cl- Channels in Cultured Corneal Endothelial Cells. Exp Eye Res. 1999 Feb;68(2):165-77.

Srinivas, S.P., J.A. Bonanno, B. Hughes, Assessment of swelling-activated Cl- channels using the halide-sensitive fluorescent indicator 6-methoxy-N-(3-sulfopropyl)quinolinium. Biophysical Journal 75:115-23 (1998).

McNamara, N.A., R.E. Fusaro, R.J. Brand, K.A. Polse and S.P. Srinivas. Measurement of Corneal Epithelial Permeability to Fluorescein: A Repeatibility Study. Invest. Opthalmol. Vis. Sci. 38(9):1830-9 (1997).

Srinivas, S.P., J.A. Bonanno, Measurement of Changes in Cell Volume Based on Fluorescence Quenching, American Journal of Physiology, 272:C1405-C1414 (1997).

Bonanno, J.A; Srinivas, S.P. cAMP activated Anion Channels in Cultured Bovine Corneal Endothelium. Experimental Eye Research, 64:953-962 (1997).

Bonanno, J.A; Srinivas, S.P.; Brown, M. Effect of acetazolamide on intracellular pH and bicarbonate transport in bovine corneal endothelium. Experimental Eye Research, 60:425-434, (1995).

Maurice, D.M; Srinivas, S.P. Fluorometric measurement of light absorption by the rabbit cornea. Experimental Eye Research, 58:409-413, (1994).

Srinivas, S.P., In situ Measurement of Fluorescein Release by Collagen Shields in Human Eyes, Current Eye Research, 1994.

Srinivas, S.P. and D. Maurice, A Microfluorometer for Measuring Diffusion across the Cornea, IEEE Transactions Biomedical Engineering, 39:1283-1291, (1992).

Maurice, D M; Srinivas, S.P. Use of fluorometry in assessing the efficacy of a cation-sensitive gel as an ophthalmic vehicle: Comparison with scintigraphy. Journal Pharmaceutical Sciences, 81:615-619, (1992).

Srinivas, S.P., R. Mutharasan and G. Rao, Redox Potential in Anaerobic and Microaerobic Fermentation, In: Handbook on Anaerobic Fermentation, Ed: L. Erickson et al., p147-186, Marcel Dekker Publishers, NY (1988).

Srinivas, S.P. and R. Mutharasan, Inner Filter Effect and its Interference in Culture Fluorescence Measurements, Biotechnology and Bioengineering, 30:769-778, (1987).

Srinivas, S.P. and R. Mutharasan, Culture Fluorescence Characteristics and its Metabolic Significance in ABE Fermentation, Biotechnology Letters, 9:139-143, (1986).

Srinivas, S.P., P.R. Krishnaswamy and P. Deshapande, Extension of Nichols Chart for Closed Loop Identification of Open Loop Control Systems, American Institute of Chemical Engineers Journal, 30:684-687, (1984).

Research
Dr. S.P. Srinivas' current research interests are (1) regulation of barrier integrity of corneal endothelium, (2) regulation of aqueous humor outflow by trabecular meshwork cells, and (3) pharmacokinetics of topical drugs to the eye.
Barrier Integrity of Ocular Epithelial and Endothelial Cells
To determine the role of actin cytoskeleton in the regulation of barrier integrity of the corneal epithelia, retinal endothelial cells, and RPE during inflammatory stress. The results would be useful in the development of pharmacological strategies to overcome barrier dysfunction involving corneal edema, diabetic retinopathy, and AMD.
Pharmacokinetics of Topical Drugs to the Eye
 To record transient concentration vs. depth profiles of fluorescein and related molecules (referred to as topical drug analogs) across rabbit corneas after topical application. Such profiles will form the basis for development of noncompartmental models which would be useful for prediction of pharmacokinetics of topical drugs based on their physico-chemical properties alone.