Rebecca M. Sappington-Calkins, Ph.D.

Associate Professor

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Faculty Appointments
Associate Professor of Ophthalmology & Visual Sciences Associate Professor of Pharmacology
Ph.D., NEUROSCIENCE, University of Rochester, Rochester, New YorkM.S., NEUROSCIENCE, University of Rochester, Rochester, New YorkB.S., Washington College , Chestertown, Maryland
Office Address
Vanderbilt University Medical Center
11420 Medical Research Building IV
2215B Garland Avenue, Room 11420
Nashville, TN 37232-0654
Research Description
Our research interest is neuroinflammation in degenerative disease. The laboratory focuses on the impact of neuronal-glial signaling in glaucoma, one of the leading causes of blindness worldwide. Vision loss in glaucoma is caused by degeneration of retinal ganglion cells (RGCs) and is often associated with elevated intraocular pressure. Although glaucomatous pathology targets RGCs, glial cells, which support RGC health and function, may also play a role in disease onset and progression. Using a variety of techniques, we examine early events in signal transduction that underlie RGC and glial responses to elevated pressure both in vitro and in vivo. We are currently pursuing interleukin-6 (IL-6), an inflammatory cytokine, as a component of RGC-glial signaling that may modulate both glial reactivity and RGC survival in glaucoma.
Research Keywords
My research specialty is neuronal-glial interactions and neuroinflammation in retinal disease.
Duncan DS, McLaughlin WM, Vasilakes N, Echevarria FD, Formichella CR, Sappington RM. Constitutive and Stress-induced Expression of CCL5 Machinery in Rodent Retina. J Clin Cell Immunol [print-electronic]. 2017 Jun; 8(3): PMID: 28936366, PMCID: PMC5604884, DOI: 10.4172/2155-9899.1000506, ISSN: 2155-9899.

Echevarria FD, Formichella CR, Sappington RM. Interleukin-6 Deficiency Attenuates Retinal Ganglion Cell Axonopathy and Glaucoma-Related Vision Loss. Front Neurosci. 2017; 11: 318. PMID: 28620279, PMCID: PMC5450377, DOI: 10.3389/fnins.2017.00318, ISSN: 1662-4548.

Lambert WS, Carlson BJ, Formichella CR, Sappington RM, Ahlem C, Calkins DJ. Oral Delivery of a Synthetic Sterol Reduces Axonopathy and Inflammation in a Rodent Model of Glaucoma. Front Neurosci. 2017; 11: 45. PMID: 28223915, PMCID: PMC5293777, DOI: 10.3389/fnins.2017.00045, ISSN: 1662-4548.

Zhang Y, Dodson KH, Fischer R, Wang R, Li D, Sappington RM, Xu YQ. Probing electrical signals in the retina via graphene-integrated microfluidic platforms. Nanoscale [print-electronic]. 2016 Dec 12/7/2016; 8(45): 19043-9. PMID: 27812594, PMCID: PMC5115917, DOI: 10.1039/c6nr07290a, ISSN: 2040-3372.

Echevarria FD, Rickman AE, Sappington RM. Interleukin-6: A Constitutive Modulator of Glycoprotein 130, Neuroinflammatory and Cell Survival Signaling in Retina. J Clin Cell Immunol [print-electronic]. 2016 Aug; 7(4): PMID: 27747134, PMCID: PMC5061045, DOI: 10.4172/2155-9899.1000439, ISSN: 2155-9899.

Bond WS, Hines-Beard J, GoldenMerry YL, Davis M, Farooque A, Sappington RM, Calkins DJ, Rex TS. Virus-mediated EpoR76E Therapy Slows Optic Nerve Axonopathy in Experimental Glaucoma. Mol. Ther [print-electronic]. 2016 Feb; 24(2): 230-9. PMID: 26502777, PMCID: PMC4817814, PII: S1525-0016(16)30329-X, DOI: 10.1038/mt.2015.198, ISSN: 1525-0024.

Dodson KH, Echevarria FD, Li D, Sappington RM, Edd JF. Retina-on-a-chip: a microfluidic platform for point access signaling studies. Biomed Microdevices. 2015 Dec; 17(6): 114. PMID: 26559199, PMCID: PMC4707151, PII: 10.1007/s10544-015-0019-x, DOI: 10.1007/s10544-015-0019-x, ISSN: 1572-8781.

Lee SJ, Duncan DS, Echevarria FD, McLaughlin WM, Hatcher JB, Sappington RM. Pressure-Induced Alterations in PEDF and PEDF-R Expression: Implications for Neuroprotective Signaling in Glaucoma. J Clin Exp Ophthalmol [print-electronic]. 2015 Oct; 6(5): PMID: 26807306, PMCID: PMC4721587, DOI: 10.4172/2155-9570.1000491, ISSN: 2155-9570.

Sappington RM, Sidorova T, Ward NJ, Chakravarthy R, Ho KW, Calkins DJ. Activation of transient receptor potential vanilloid-1 (TRPV1) influences how retinal ganglion cell neurons respond to pressure-related stress. Channels (Austin). 2015; 9(2): 102-13. PMID: 25713995, PMCID: PMC4594535, DOI: 10.1080/19336950.2015.1009272, ISSN: 1933-6969.

Weitlauf C, Ward NJ, Lambert WS, Sidorova TN, Ho KW, Sappington RM, Calkins DJ. Short-term increases in transient receptor potential vanilloid-1 mediate stress-induced enhancement of neuronal excitation. J. Neurosci. 2014 Nov 11/12/2014; 34(46): 15369-81. PMID: 25392504, PMCID: PMC4228139, PII: 34/46/15369, DOI: 10.1523/JNEUROSCI.3424-14.2014, ISSN: 1529-2401.

Formichella CR, Abella SK, Sims SM, Cathcart HM, Sappington RM. Astrocyte Reactivity: A Biomarker for Retinal Ganglion Cell Health in Retinal Neurodegeneration. J Clin Cell Immunol. 2014 Feb; 5(1): PMID: 25133067, PMCID: PMC4131747, DOI: 10.4172/2155-9899.1000188, ISSN: 2155-9899.

Echevarria F, Walker C, Abella S, Won M, Sappington R. Stressor-dependent Alterations in Glycoprotein 130: Implications for Glial Cell Reactivity, Cytokine Signaling and Ganglion Cell Health in Glaucoma. J Clin Exp Ophthalmol. 2013 Jun 6/30/2013; 4(3): PMID: 25018894, PMCID: PMC4091850, ISSN: 2155-9570.

Sims SM, Holmgren L, Cathcart HM, Sappington RM. Spatial regulation of interleukin-6 signaling in response to neurodegenerative stressors in the retina. Am J Neurodegener Dis. 2012; 1(2): 168-79. PMID: 23024928, PMCID: PMC3560463, ISSN: 2165-591X.

Chen H, Wei X, Cho KS, Chen G, Sappington R, Calkins DJ, Chen DF. Optic neuropathy due to microbead-induced elevated intraocular pressure in the mouse. Invest. Ophthalmol. Vis. Sci. 2011 Jan 1/5/2011; 52(1): 36-44. PMID: 20702815, PMCID: PMC3053285, PII: iovs.09-5115, DOI: 10.1167/iovs.09-5115, ISSN: 1552-5783.

Joos KM, Li C, Sappington RM. Morphometric changes in the rat optic nerve following short-term intermittent elevations in intraocular pressure. Invest. Ophthalmol. Vis. Sci [print-electronic]. 2010 Dec; 51(12): 6431-40. PMID: 20688743, PMCID: PMC3055763, PII: iovs.10-5212, DOI: 10.1167/iovs.10-5212, ISSN: 1552-5783.

Crish SD, Sappington RM, Inman DM, Horner PJ, Calkins DJ. Distal axonopathy with structural persistence in glaucomatous neurodegeneration. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2010 Mar 3/16/2010; 107(11): 5196-201. PMID: 20194762, PMCID: PMC2841892, PII: 0913141107, DOI: 10.1073/pnas.0913141107, ISSN: 1091-6490.

Sappington RM, Carlson BJ, Crish SD, Calkins DJ. The microbead occlusion model: a paradigm for induced ocular hypertension in rats and mice. Invest. Ophthalmol. Vis. Sci [print-electronic]. 2010 Jan; 51(1): 207-16. PMID: 19850836, PMCID: PMC2869054, PII: iovs.09-3947, DOI: 10.1167/iovs.09-3947, ISSN: 1552-5783.

Sappington RM, Sidorova T, Long DJ, Calkins DJ. TRPV1: contribution to retinal ganglion cell apoptosis and increased intracellular Ca2+ with exposure to hydrostatic pressure. Invest. Ophthalmol. Vis. Sci [print-electronic]. 2009 Feb; 50(2): 717-28. PMID: 18952924, PMCID: PMC3549616, PII: iovs.08-2321, DOI: 10.1167/iovs.08-2321, ISSN: 1552-5783.

Wax MB, Tezel G, Yang J, Peng G, Patil RV, Agarwal N, Sappington RM, Calkins DJ. Induced autoimmunity to heat shock proteins elicits glaucomatous loss of retinal ganglion cell neurons via activated T-cell-derived fas-ligand. J. Neurosci. 2008 Nov 11/12/2008; 28(46): 12085-96. PMID: 19005073, PMCID: PMC2683273, PII: 28/46/12085, DOI: 10.1523/JNEUROSCI.3200-08.2008, ISSN: 1529-2401.

Sappington RM, Calkins DJ. Contribution of TRPV1 to microglia-derived IL-6 and NFkappaB translocation with elevated hydrostatic pressure. Invest. Ophthalmol. Vis. Sci [print-electronic]. 2008 Jul; 49(7): 3004-17. PMID: 18362111, PMCID: PMC4139938, PII: iovs.07-1355, DOI: 10.1167/iovs.07-1355, ISSN: 1552-5783.

Sappington RM, Calkins DJ. Pressure-induced regulation of IL-6 in retinal glial cells: involvement of the ubiquitin/proteasome pathway and NFkappaB. Invest. Ophthalmol. Vis. Sci. 2006 Sep; 47(9): 3860-9. PMID: 16936098, PII: 47/9/3860, DOI: 10.1167/iovs.05-1408, ISSN: 0146-0404.

Sappington RM, Chan M, Calkins DJ. Interleukin-6 protects retinal ganglion cells from pressure-induced death. Invest. Ophthalmol. Vis. Sci. 2006 Jul; 47(7): 2932-42. PMID: 16799036, PII: 47/7/2932, DOI: 10.1167/iovs.05-1407, ISSN: 0146-0404.

Inman DM, Sappington RM, Horner PJ, Calkins DJ. Quantitative correlation of optic nerve pathology with ocular pressure and corneal thickness in the DBA/2 mouse model of glaucoma. Invest. Ophthalmol. Vis. Sci. 2006 Mar; 47(3): 986-96. PMID: 16505033, PII: 47/3/986, DOI: 10.1167/iovs.05-0925, ISSN: 0146-0404.

Calkins DJ, Sappington RM, Hendry SH. Morphological identification of ganglion cells expressing the alpha subunit of type II calmodulin-dependent protein kinase in the macaque retina. J. Comp. Neurol. 2005 Jan 1/10/2005; 481(2): 194-209. PMID: 15562509, DOI: 10.1002/cne.20368, ISSN: 0021-9967.

Sappington RM, Pearce DA, Calkins DJ. Optic nerve degeneration in a murine model of juvenile ceroid lipofuscinosis. Invest. Ophthalmol. Vis. Sci. 2003 Sep; 44(9): 3725-31. PMID: 12939285, ISSN: 0146-0404.