Molecular and cellular mechanisms that underlie the regulation of aqueous humor
outflow in the human eye; including receptor activation, second
messenger signaling, ion and water transport, and secretory function
Glaucoma is the second leading cause of blindness in the United
States. In most cases of glaucoma, an elevated intraocular pressure
is thought to compress nerve axons in the retina and result in
a loss of vision. The cause of elevated intraocular pressure
resides in the primary outflow path of the eye, the trabecular
meshwork and the inner wall of Schlemm’s canal. Many hypotheses
concerning the mechanism(s) of aberrant aqueous outflow in this
region have been formulated and tested, however, the precise mechanism(s)
are still not clear. The focus of my research is to determine
the molecular and cellular mechanisms that underlie normal and
abnormal maintenance of aqueous humor outflow.
Currently, I study two candidate proteins for glaucoma, aquaporin-1
and myocilin, and am interested in their functional role in the
cells of the outflow pathway of the human eye. My approach
is to design and construct recombinant molecules that contain
all or part of aquaporin-1 or myocilin and to study their heterologous
expression in transformed cells and primary cells of the outflow
pathway. For example, I have made adenoviral constructs
that code for sense and antisense aquaporin-1 RNA, and made chimeras
that are composed of green fluorescent protein plus different
segments of myocilin. My aim is to functionally characterize
these and other candidate proteins of the outflow pathway in order
to clarify their contribution to aqueous humor outflow.
WD Stamer, K Peppel, ME O’Donnell, BC Roberts, F Wu, and
DL Epstein. (2001) Expression of Aquaporin-1 in human trabecular
meshwork cells: Role in volume regulation. Invest. Ophthalmol.
Vis. Sci. 42: 1803-1811. Chosen for the “Editors selection”
in International Glaucoma Review III/2, 2002.
WD Stamer, S.F. Golightly, Y. Hosohata, E. P. Ryan, E. Varga,
R.J. Noecker A.C. Porter, C.C. Felder and H.I. Yamamura. (2001)
CB1 cannabinoid receptor expression, activation and detection
of endogenous ligand in trabecular meshwork and ciliary process
tissues. Eur J. Pharmacol, 431: 277-286.
AJ Yool, OH Brokl, TL Pannabecker, WH Dantzler and WD Stamer.
(2002) Tetraethylammonium block of water flux in Aquaporin-1 channels
expressed in kidney thin limbs of Henle's loop and a kidney-derived
cell line, BMC Physiol, 2:4.
WD Stamer, BC Roberts and DL Epstein: Hydraulic pressure
stimulates adenosine 3’,5’-cyclic monophosphate accumulation in
endothelial cells from Schlemm’s Canal. Invest. Ophthalmol. Vis.
Sci , 40:1983-1988, 1999.
WD Stamer, BC Roberts, DN Howell and DL Epstein: Isolation,
culture and characterization of endothelial cells from Schlemm’s
canal. Invest. Ophthalmol. Vis. Sci. 39 1804-1812, 1998.
WD Stamer, RW Snyder and JW Regan: Characterization of
the transmembrane orientation of aquaporin-1 using antibodies
to fusion proteins. Biochemistry, 35: 16313-16318, 1996.
AJ Yool, WD Stamer and JW Regan. Forskolin stimulation
of water and cation permeability in aquaporin-1 water channels.
Science, 273: 1216-1218, 1996.
