OHSU

Graduate Studies Faculty

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Ted S. Acott, PhD

Professor
Admin Unit: SOM-Ophthalmology Department
Phone: 503.494.8455
Lab Phone: 503.494.5199
Fax: 503.418.2399
Office: BRB Rm 217
Mail Code: CERES
Programs:
Biochemistry & Molecular Biology
Program in Molecular & Cellular Biosciences
Research Interests:
Molecular etiology of glaucoma; extracellular matrix turnover; signal transduction; RNAi silencing and alternative mRNA splicing; molecular mechanisms of intraocular pressure homeostasis; molecular mechanisms of genetic causal agents for glaucoma » Click here for more about Dr. Acott's research » PubMed Listing
Preceptor Rotations
Dr. Acott has not indicated availability for preceptor rotations at this time.
Faculty Mentorship
Dr. Acott has not indicated availability as a mentor at this time.
Profile

Ted Acott received his BS in Chemistry in 1966 and PhD in Biochemistry in 1974 from the University of Wyoming. After Postdoctoral studies in Biophysical Chemistry and Pharmacology at the University of Minnesota and in Reproductive Physiology at the Oregon Regional Primate Research Center in Beaverton, OR, he accepted a position as Assistant Scientist at the Primate Center in 1978. In 1982, he moved to OHSU in the Department of Ophthalmology with a joint appointment in Department of Biochemistry. In 1999 he was promoted to Professor in Ophthalmology and in Biochemistry and Molecular Biology.

Research Interests

Glaucoma is a blinding optic neuropathy affecting over 67 million persons worldwide. The primary risk factor for glaucoma is elevated intraocular pressure (IOP), caused by increased resistance to aqueous humor outflow from the eye through a small filtration tissue called the trabecular meshwork, which surrounds the inner circumference of the cornea. The causes of this increase in the outflow resistance are not clear. The resistance is comprised of a thin amorphous layer of extracellular matrix (ECM) with trabecular meshwork cells imbedded within it and with Schlemm’s canal inner wall cells overlaying it on the downstream side.

The first major project is to understand the molecular etiology of glaucoma by asking why most people do not get glaucoma, even at advanced ages. We found that a well-developed IOP homeostasis mechanism exists by which these trabecular meshwork cells sense pressure changes as mechanical stretching or distortion of their ECM and respond by increasing and modifying ECM turnover. Specialized dynamic focal ECM turnover units were identified on these cells, which we have named podosome- or invadopodia-like structures (PILS). These PILS facilitate carefully-regulated adjustments of the outflow resistance without producing tissue disorganization. Investigating the molecular organization and functional details of these structures is the current focus of this project.

The second major project has been to understand the molecular mechanism of a common treatment for glaucoma, called laser trabeculoplasty. This project has evolved into our current focus on understanding the molecular composition and structural organization of the actual outflow resistance. Versican, a large proteoglycan, appears to provide the central resistance component. It interacts with a variety of ECM binding and organizational proteins, such as fibronectin, tenascin C, syndecan 2, thrombospondin 1 and 2, and collagen XII and XIV. Hyaluronan and several cell surface receptors are also integrally involved in forming and organizing this complex resistance structure. Agents which change the outflow resistance, modulate a number of these ECM macromolecules and their turnover, initiated by members of the matrix metalloproteinase family and the ADAMTS (a disintegrin and metalloproteinase with thrombospondin domains) family. Studies to further unravel this complex ECM organization and how changes in it modify the outflow resistance are ongoing.

Recent Selected Publications

 

Keller KE, Bradley JM, Kelley MJ, Acott TS. Effects of modifiers of glycosaminoglycan biosynthesis on outflow facility in perfusion culture. Invest Ophthalmol Vis Sci 49:2495-2505, 2008.

 

Aga M, Bradley JM, Keller KE, Kelley MJ, Acott TS. Specialized podosome- or invadopodia-like structures (PILS) for focal trabecular meshwork extracellular matrix turnover. Invest Ophthalmol Vis Sci, 49:5353-5365, 2008.

 

Keller KE, Bradley JM, Acott TS. Differential effects of ADAMTSs -1, -4, and -5 in the Trabecular Meshwork. Invest Ophthalmol Vis Sci 50: (Epub at PubMed ahead of print), 2009.

 

Acott TS, Kelley MJ. Extracellular Matrix in the Trabecular Meshwork (Review). Exp Eye Res 86:543-561, 2008.

 

Keller KE, Aga M, Bradley JM, Kelley MJ, Acott TS. Extracellular matrix turnover and outflow resistance (Reivew). Exp Eye Res 88:676-682, 2009.

Vittal V, Rose A, Gregory KE, Kelley MJ, Acott TS. Changes in gene expression by trabecular meshwork cells in response to mechanical stretch. Invest Ophthalmol Vis Sci. 46:2857-2868,2005.

Keller KE, Kelley MJ, Acott TS. Extracellular matrix gene alternative splicing by trabecular meshwork cells in response to mechanical stretch. Invest Ophthalmol Vis Sci 48: 1164-1172, 2007.