Thyroid Gland Dysfunction and Keratoconus
Zisis Gatzioufas, Berthold SeitzZisis Gatzioufas, Berthold Seitz
Department of OphthalmologyDepartment of OphthalmologyUniversity of Saarland UKS, GermanyUniversity of Saarland UKS, Germany
Chairman: Prof. Dr. B. SeitzChairman: Prof. Dr. B. Seitz
The authors have no financial interest in the subject matter of this poster
Introduction
● Thyroid hormones are important for corneal development (Coulombre, 1958)
● Keratoconus may follow thyroidectomy (King, 1953)
● Thyroxine is important for collagen synthesis (Drozdz, 1979)
● Hypothyroxinaemia may accelerate the progress
of keratoconus and cause acute hydrops (Gatzioufas, 2008)
Purpose
Is there an evidence-based association between keratoconus and thyroid gland dysfunction?
Aim: to investigate the possible association between keratoconus and thyroid disease on a clinical and molecular level.
Keratoconus Thyroid gland dysfunction??
Methods
Study group:Study group: 154 patients with keratoconus154 patients with keratoconus
● Endocrinological screening
Clinical study
Basic research study
Target protein: thyroxine receptor (THR)
Methods: Immunohistochemistry – Western blotting – Cell biology
Results - Endocrinological screening
GroupsHypothyroidism
Men (%) Women (%) Total (%)
Keratoconus group 5.3 23.3 13.6
Control group 1.0 3.3 1.9
General population 0.2 2.0 1.2
Increased incidence of hypothyroidism in the keratoconus group compared to control group (p<0.001, t-test)
• The incidence of positive antiTPOAb and/or antiTgAb was significantly increased in patients with keratoconus (25.3%) compared to control subjects (6.4%) (p<0.001, t-test)
Results - Immunoassay
Keratoconus group:
• HTD-group: 11.8±6.2 nmol/l
• n-HTD-group: 10.9±5.1 nmol/l
Control group: 3.0±1.7 nmol/l HTD n-HTD C
Thyroxine concentration in tear film
HTD: patients with keratoconus and hypothyroidism; n-HTD: patients with keratoconus but without hypothyroidism; C: control group
Results - Immunohistochemistry
Dapi Cy2 Overlay
NC THR
KC THR
Control
KC THR
NC: normal cornea; KC: keratoconus cornea; THR: thyroxine receptors
● Both NC and KC expressed THR.
● THR signal was detected in epithelium and stroma.
● No signal was observed in corneal endothelium.
Results – Immunohistochemistry/Western blotting
KC: keratoconus cornea; Normal: normal cornea; THR: thyroxine receptors
● Epithelial expression of THR in KC was comparable to that in normal cornea .
● Stromal expression of THR in KC was upregulated compared to that in normal cornea.
● Densitometry-analysis of Western blotting results revealed a 2-fold increase of THR in KC stroma compared to normal corneal stroma.
• Monkey corneas (Macaca fascicularis) were cultivated in vitro
• Corneal epithelium was separated from corneal stroma
• Cells were treated with different thyroxine-concentrations (TH)
Stroma
Epithelium
Stroma+Epithelium
no TH + TH100 µg/l
+ TH500 µg/l
+ TH1 mg/l
Results – Corneal cell culture
Results – Corneal cell culture
0
500
1000
1500
2000
2500
No-TH TH 100 µg TH 500 µg TH 1000 µg
Cel
ls/m
m2
Stroma
Epithelium
EpitheliumStroma
● Thyroxine stimulated the proliferation of both epithelial and stromal cells in vitro.
● The stimulation rate was dosage-dependent.
● A plateau of 2500 cell/mm2 was observed in epithelial cell cultures, while stromal cell cultures demonstrated a plateau of 1740 cell/mm2.
Conclusions
The incidence of hypothyroidism is significantly increased in keratoconus.
Thyroxine concentration in tear film is significantly increased in patients with keratoconus.
Human cornea expresses thyroxine receptors (THR) in epithelium and stroma.
THR expression in corneal stroma is significantly increased in keratoconus.
Thyroxine stimulates the proliferation of epithelial and stromal corneal cells in vitro.
