Graefe's Arch Clin Exp Ophthalmol (1999)
237:231±240 Springer-Verlag 1999 CLINICAL INVESTIGATION
Keith G. Duncan
Michele D. Jumper
Ralff C. J. Ribeiro
Kathy R. Bailey
Paul M. Yen
Akira Sugawara
Ashmi Patel
Robert Stern
William W. Chin
John D. Baxter
Daniel M. Schwartz
Human trabecular meshwork cells
as a thyroid hormone target tissue:
presence of functional thyroid hormone
receptors
Received: 5 February 1998
Revised version received: 2 June 1998
Accepted: 6 July 1998
K.G. Duncan ´ R.C.J. Ribeiro
K.R. Bailey ´ J.D. Baxter
Metabolic Research Unit,
University of California, San Francisco,
California, USA
K.G. Duncan ´ M.D. Jumper
A. Patel ´ D.M. Schwartz (
)
)
Department of Ophthalmology,
University of California, San Francisco,
10 Kirkham Street, Box 0730,
San Francisco, CA 94143, USA
Tel. 001-415-476-1887
Fax 001-415-476-0336
P.M. Yen ´ A. Sugawara ´ W.W. Chin
Division of Genetics,
Department of Medicine,
Brigham and Women's Hospital,
Howard Hughes Medical Institute,
Harvard Medical School, Boston,
Massachusetts, USA
R. Stern
Department of Pathology,
University of California, San Francisco,
California, USA
Abstract. l Purpose: To deter-
mine whether human trabecular
meshwork cells (HTM) are a po-
tential target tissue for thyroid hor-
mone (3,3©,5-triiodothyronine, T
3
).
l Methods: Cultured HTM were as-
sayed for the presence of thyroid
hormone receptors (TRs) and retinoid
X receptors (RXRs) by reverse-tran-
scriptase polymerase chain reaction
(RT-PCR) to detected TR and RXR
mRNA, and by immunohistochemis-
try to detect nuclear TR and RXR
proteins. Functionality of the TR was
determined by analysis of
125
I-T
3
binding affinity and capacity in HTM
nuclear extracts. Effects of T
3
on
modulation of hyaluronic acid (HA)
levels in HTM were measured as a
function of dose and duration of T
3
administration. l Results: Analysis
of RT-PCR and immunohistochem-
istry demonstrated that cultured HTM
expressed TRa1, TRa2, and TRb1
but not TRb2; and RXRa but not
RXRb and RXRg isoforms. Satura-
tion binding and analysis of
125
I-T
3
to
HTM nuclear extracts revealed K
d
of
57 pM. The number of T
3
binding
sites extrapolated from a Scatchard
plot was 7.310
10
/mg of HTM nuclear
protein extract. T
3
supplementation
reduced the concentration of HA in
the cell medium by 32±43% com-
pared to cells grown in the absence
of T
3
. l Conclusions: Cultured HTM
express three TR isoforms and one
RXR isoform, bind T
3
with an affin-
ity similar to that of TR in responsive
cells, and modulate their HA pro-
duction in response to T
3
. These
findings indicate that the human tra-
becular meshwork tissue has the ca-
pacity to respond to thyroid hor-
mones.
Introduction
There has been interest in the association between prima-
ry open-angle glaucoma (POAG) and hypothyroidism
since the report by Hertel in 1920 of two patients with
both of these disorders [17] in whom systemic thyroid
hormone replacement resulted in normalization of the in-
traocular pressure (IOP). Numerous subsequent studies
addressed this association [4, 7, 8, 14, 16, 27, 35, 38,
45, 47, 51±53], with conflicting conclusions. Supporting
an association between hypothyroidism and POAG,
Smith et al. used currently accepted methods of evaluat-
ing thyroid function and found that 23.4% or 64 patients
with POAG were hypothyroid compared to 4.7% of age-
matched controls [53]. In patients with newly diagnosed
hypothyroidism, Smith et al. observed that 14/25 (56%)
had abnormal outflow facility [52]. Systemic replace-
ment with thyroid hormone resulted in euthyroid status
in all patients and normalization of outflow facility in
all but one patient. McDaniel and Besada have also de-
scribed one hypothyroid patient whose IOP was reduced
with systemic thyroid replacement therapy [34]. Gillow
et al., using similar methods of evaluating thyroid func-