Degrees
B.Sc,. McGill University, 1986
Ph.D., Institute of Ophthalmology, University College London, 1994

Honors
1988 Fight for Sight UK Studentship Award
1992 Royal National Institute for the Blind Fellowship
1994 International Society of Eye Research Award
1995 NRSA Fellowship in Neuroscience
1996 NRSA Fellowship in Respiratory Physiology
2002 University Research Foundation Award

Professional Affiliations
American Physiological Society
Association for Research in Vision and Ophthalmology
Salt and Water Club

Research Description
The research of this laboratory is concerned with the ability of purinergic and glutaminergic neurotransmitter systems to modify ocular health. These neurotransmitters were among the first to develop evolutionarily and can be released from non-specialized cell types such as epithelial and glial cells in additional to neurons. Research is presently focused upon how these neurotransmitters alter the function of retinal pigment epithelial cells in the outer retina, and how they affect retinal ganglion cell viability under glaucomatous conditions.

The retinal pigment epithelium supports the function of the photoreceptor outer segments and we believe the purines ATP and adenosine, along with glutamate, can modify their interaction. The retinal pigment epithelium can release ATP into the subretinal space separating the two cell types, and the laboratory is currently investigating how this released ATP is converted into adenosine by ecto-enzymes, and how the adenosine thus produced can modulate RPE physiology. We are particularly interested in the pathways for ATP release and the regulation of ecto-enzyme activity. This information may enhance our understanding of the communication between the RPE and photoreceptors under physiologic and pathophysiologic conditions.

Purines and glutamate are also critical for the health of retinal ganglion cells. The ganglion cells convey the visual message from the eye to the brain, and are the primary cell lost after the elevations of intraocular pressure common in glaucoma. Currently, the lab is investigating whether elevations of ATP follow the increase in intraocular pressure found in glaucoma, and the role of P2X7 receptors for ATP in ganglion cell death. The cellular mechanisms which link P2X7 stimulation to cell death may differ in neurons and are being investigated. The neuroprotective potential of P2X7 antagonists, and of adenosine agonists are being examined. We are also concerned with the contribution of glutamate in this process, and whether its role is a primary or secondary in response to changes in ATP levels.

Representative Publications

Avila, M.Y., C.H. Mitchell, R.A. Stone, and M.M. Civan. 2003. Non-invasive assessment of aqueous humor turnover in the mouse eye. Invest.Ophthalmol. Vis. Sci. 44:722-727.

Mitchell, C.H., J.C. Fleischhauer, W.D. Stamer, K. Peterson-Yantorno and M.M. Civan. Human trabecular meshwork cell volume regulation. 2002. Am. J. Physiol. 283:315-326.

Zhang, X., C.H. Mitchell, R. Wen and A.M. Laties. 2002. Nerve fiber layer splaying at vascular crossings. Invest. Ophthalmol. Vis. Sci.43: 2063-2066.

Mitchell, C.H. 2001. Release of ATP by a human retinal pigment epithelial cell line: possible autocrine stimulation into the subretinal space. J. Physiol. 534: 193-202.

Mitchell, C.H., K. Peterson-Yantorno, M. Coca-Prados and M.M. Civan. 2000. Tamoxifen and ATP synergistically activate Cl- release by cultured bovine pigmented ciliary epithelial cells. J. Physiol. 525.1, 183-193.

Mitchell, C.H., K. Peterson-Yantorno, D.A. Carré, A.M. McGlinn, M. Coca-Prados, R.A. Stone and M.M. Civan. 1999. A3 adenosine receptors regulate Cl- channels of nonpigmented ciliary epithelial cells. Am. J. Physiol. 276:C659-666.

Mitchell, C.H., D.A. Carré, A.M. McGlinn, R.A. Stone and M.M. Civan. 1998. A release mechanism for stored ATP in ocular ciliary epithelial cells. Proceed. Nat. Acad. Sci. 95: 7174-7178.

Mitchell, C.H., L. Wang and T.J.C. Jacob. 1997. A large-conductance chloride channel in pigmented ciliary epithelial cells activated by GTPgS. J. Membr. Biol: 158:167-175.

Mitchell, C.H., J.J. Zhang, L. Wang and T.J.C. Jacob. 1997. Volume-sensitive chloride currents in pigmented ciliary epithelial cells: role of phospholipases. Am. J. Physiol. 272: C212-C222.

Click here for a full list of publications
(searches the National Library of Medicine's PubMed database.)