The investigator intends to explore the underlying basis of retinal ganglion cell death seen in primary open angle glaucoma. Her investigations are based on previous work that has suggested that glutamate is abnormally high in the vitreous of patients with glaucoma. She intends to explore first the relationship between vitreal glutamate concentration and glaucomatous damage. This will be carried out by gas chromatography/mass spectroscopy in the paired eyes of monkeys with monocular experimentally induced glaucoma. She intends to correlate the magnitude of the glutamate elevation with the degree of nerve fiber loss. Secondly, she presents the hypothesis that the elevation in vitreal glutamate is a consequence of a perturbation in Muller cells. Retinal Muller cells are known to play a major role in the removal of glutamate from the extracellular space, and in its subsequent metabolism. The hypothesis is therefore presented that the elevated vitreal glutamate level can be the result of alterations in the activity of Muller cells. She intends to carry out immunocytochemical analyses to assess alterations in Muller cell activity in glutamate metabolism. It is hoped, based on these findings, that an explanation will be found for the elevated level of glutamate in the vitreous, as well as identifying potential new pharmacologic agents.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY011545-03
Application #
2888531
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1997-08-01
Project End
2002-07-31
Budget Start
1999-08-01
Budget End
2002-07-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Harwerth, Ronald S; Carter-Dawson, Louvenia; Smith 3rd, Earl L et al. (2005) Scaling the structure--function relationship for clinical perimetry. Acta Ophthalmol Scand 83:448-55
Carter-Dawson, Louvenia; Shen, F Fran; Harwerth, Ronald S et al. (2004) Glutathione content is altered in Muller cells of monkey eyes with experimental glaucoma. Neurosci Lett 364:7-10
Crawford, Morris L J; Harwerth, Ronald S (2004) Ocular dominance column width and contrast sensitivity in monkeys reared with strabismus or anisometropia. Invest Ophthalmol Vis Sci 45:3036-42
Harwerth, Ronald S; Carter-Dawson, Louvenia; Smith 3rd, Earl L et al. (2004) Neural losses correlated with visual losses in clinical perimetry. Invest Ophthalmol Vis Sci 45:3152-60
Wang, Zhiqing; Li, Wei; Mitchell, Cheryl K et al. (2003) Activation of protein kinase C reduces GLAST in the plasma membrane of rat Muller cells in primary culture. Vis Neurosci 20:611-9
Harwerth, Ronald S; Crawford, M L J; Frishman, Laura J et al. (2002) Visual field defects and neural losses from experimental glaucoma. Prog Retin Eye Res 21:91-125
Carter-Dawson, Louvenia; Crawford, Morris L J; Harwerth, Ronald S et al. (2002) Vitreal glutamate concentration in monkeys with experimental glaucoma. Invest Ophthalmol Vis Sci 43:2633-7
Crawford, M L; Harwerth, R S; Smith 3rd, E L et al. (2001) Experimental glaucoma in primates: changes in cytochrome oxidase blobs in V1 cortex. Invest Ophthalmol Vis Sci 42:358-64
Carter-Dawson, L; Shen, F; Harwerth, R S et al. (1998) Glutamine immunoreactivity in Muller cells of monkey eyes with experimental glaucoma. Exp Eye Res 66:537-45