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Thyroid Gland Dysfunction and Keratoconus

Thyroid Gland Dysfunction and Keratoconus. Zisis Gatzioufas, Berthold Seitz. Department of Ophthalmology University of Saarland UKS, Germany Chairman: Prof. Dr. B. Seitz. The authors have no financial interest in the subject matter of this poster. Introduction.

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Thyroid Gland Dysfunction and Keratoconus

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  1. Thyroid Gland Dysfunction and Keratoconus Zisis Gatzioufas, Berthold Seitz Department of Ophthalmology University of Saarland UKS, Germany Chairman: Prof. Dr. B. Seitz The authors have no financial interest in the subject matter of this poster

  2. 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)

  3. Purpose Is there an evidence-based association between keratoconus and thyroid gland dysfunction? ?? Keratoconus Thyroid gland dysfunction Aim: to investigate the possible association between keratoconus and thyroid disease on a clinical and molecular level.

  4. Methods Clinical study Study group:154 patients with keratoconus Endocrinological screening Basic research study Target protein: thyroxine receptor (THR) Methods: Immunohistochemistry – Western blotting – Cell biology

  5. Results - Endocrinological screening • 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)

  6. Results - Immunoassay Thyroxine concentration in tear film 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 HTD: patients with keratoconus and hypothyroidism; n-HTD: patients with keratoconus but without hypothyroidism; C: control group

  7. Results - Immunohistochemistry Dapi Cy2 Overlay NC THR Both NC and KC expressed THR. THR signal was detected in epithelium and stroma. No signal was observed in corneal endothelium. KC THR KC THR Control NC: normal cornea; KC: keratoconus cornea; THR: thyroxine receptors

  8. Results – Immunohistochemistry/Western blotting 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. KC: keratoconus cornea; Normal: normal cornea; THR: thyroxine receptors

  9. Results – Corneal cell culture • 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 + TH 100 µg/l + TH 500 µg/l + TH 1 mg/l no TH

  10. Stroma Epithelium Cells/mm2 Epithelium Stroma Results – Corneal cell culture 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.

  11. 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.

  12. Thank you for your attention! zisis.gatzioufas@uniklinikum-saarland.de

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