Targeting Neurobiological Sensitivity to Pressure in Glaucoma

David Calkins, PhD
Vanderbilt University Medical Center (Nashville, TN)
Year Awarded:
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April 1, 2008 to March 31, 2010
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US Southeastern
Recipient of the Thomas R. Lee award for National Glaucoma Research

TRPV1: A Novel Neuroprotective Target in Glaucoma


This research is aimed at understanding how optic nerve fibers respond to eye pressure and whether blunting this response could prevent vision loss in glaucoma. The study will also help identify new drugs to reduce optic nerve loss in glaucoma by making its fibers insensitive to eye pressure.


Glaucoma is the leading cause of irreversible blindness worldwide and is estimated to afflict some 80 million people by 2020. Most people think of glaucoma as a disease about pressure in the eye, because high pressure is associated with the disease and lowering pressure often is helpful for slowing vision loss in glaucoma. In fact, glaucoma is irreversible because it damages the fibers of the optic nerve, which is part of the brain and therefore limited in its ability to heal. Our research is important because it is the first attempt to understand how these fibers respond to pressure in the eye and whether blunting this response could prevent vision loss in glaucoma. Our team is comprised of neurobiologists with expertise in how nerve fibers respond to pressure. Thus, our research will help identify new drugs that will reduce the loss of the optic nerve in glaucoma by making its fibers insensitive to pressure in the eye.


Sappington, R.M., Sidorova, T., Long, D.J. & Calkins, D.J. (2009) TRPV1: Contribution to retinal ganglion cell apoptosis and increased intracellular Ca2+ with exposure to hydrostatic pressure (Inv. Ophthal. Vis. Sci., 50, 717-728).  

Sappington, R.M., Carlson, B.J., Crish, S.D. & Calkins, D.J. (2010) The microbead occlusion model: a paradigm for induced ocular hypertension in rats and mice (Inv. Ophthal. Vis. Sci., 51, 207-216).  

Crish, S.D., Sappington, R.M., Inman, D.M, Horner, P.J., Calkins, D.J. (2010) Distal axonopathy with structural persistence in glaucomatous neurodegeneration (Proc. Nat. Acad. Sci., 107(11):5196-201).  

K.W. Ho, S.F. Juliao, B. Zhao, R.M. Sappington, D.J. Calkins. Expression of the TRPV Family in the DBA/2J Mouse Model of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2010; ARVO E-Abstract # 2125 [conference abstract]

Sappington RM, Sidorova TN, Calkins DJ. Trpv1 contributes to pressure-induced death and disruption of axonal transport in RGCs. Invest. Ophthalmol. Vis. Sci. 2008; ARVO E-Abstract 5481. [conference abstract]