TY - JOUR
T1 - The effect of prostaglandin analogue bimatoprost on thyroid-associated orbitopathy
AU - Choi, Catherine J.
AU - Tao, Wensi
AU - Doddapaneni, Ravi
AU - Acosta-Torres, Zenith
AU - Blessing, Nathan W.
AU - Lee, Bradford W.
AU - Pelaez, Daniel
AU - Wester, Sara T.
N1 - Funding Information:
The authors thank David Tse, MD, FACS, for his mentoship and support of this study. Supported by National Institutes of Health Center Core Grant P30EY014801, Research to Prevent Blindness Unrestricted Grant, Inc. (New York, NY, USA) and the Dr. Nasser Ibrahim Al-Rashid Orbital Vision Research Fund.
Publisher Copyright:
© 2018 The Authors.
PY - 2018/12
Y1 - 2018/12
N2 - PURPOSE. We characterize the effect of bimatoprost on orbital adipose tissue in thyroid-associated orbitopathy (TAO) with clinicopathologic correlation. METHODS. Orbital adipose-derived stem cells (OASCs) from types 1 and 2 TAO and control patients with and without exposure to 1 lm bimatoprost were examined via immunohistochemistry, RT-PCR, and Western blot for cell viability, migration capacity, lipid content, adipocyte morphology, mitochondrial content, and levels of adipogenic markers. A retrospective chart review was performed for clinicopathologic correlation. In mice, optical coherence tomography and pattern electroretinography were performed at baseline and at 1 month following a retrobulbar injection of bimatoprost, followed by orbital exenteration for histopathologic examination. RESULTS. Types 1 and 2 TAO-derived cells had a significantly higher migration capacity and lipid content than those of healthy controls. With the addition of bimatoprost, types 1 and 2 TAO and control adipocytes exhibited a significant decrease in lipid content with morphologic transformation into smaller and multilocular lipid droplets, and an increase in mitochondrial load and UCP-1 expression consistent with an increase in brown adipose tissue turnover. Retrobulbar injection of bimatoprost in mice did not alter the gross morphology, retinal thickness, or ganglion cell function in vivo. CONCLUSIONS. Bimatoprost inhibits adipogenesis in OASCs and upregulates pathways involved in the browning of adipocytes. Furthermore, retrobulbar injection of bimatoprost is tolerated without immediate adverse effects in mice. Our results suggest a potential future application of prostaglandin analogues in the treatment of TAO.
AB - PURPOSE. We characterize the effect of bimatoprost on orbital adipose tissue in thyroid-associated orbitopathy (TAO) with clinicopathologic correlation. METHODS. Orbital adipose-derived stem cells (OASCs) from types 1 and 2 TAO and control patients with and without exposure to 1 lm bimatoprost were examined via immunohistochemistry, RT-PCR, and Western blot for cell viability, migration capacity, lipid content, adipocyte morphology, mitochondrial content, and levels of adipogenic markers. A retrospective chart review was performed for clinicopathologic correlation. In mice, optical coherence tomography and pattern electroretinography were performed at baseline and at 1 month following a retrobulbar injection of bimatoprost, followed by orbital exenteration for histopathologic examination. RESULTS. Types 1 and 2 TAO-derived cells had a significantly higher migration capacity and lipid content than those of healthy controls. With the addition of bimatoprost, types 1 and 2 TAO and control adipocytes exhibited a significant decrease in lipid content with morphologic transformation into smaller and multilocular lipid droplets, and an increase in mitochondrial load and UCP-1 expression consistent with an increase in brown adipose tissue turnover. Retrobulbar injection of bimatoprost in mice did not alter the gross morphology, retinal thickness, or ganglion cell function in vivo. CONCLUSIONS. Bimatoprost inhibits adipogenesis in OASCs and upregulates pathways involved in the browning of adipocytes. Furthermore, retrobulbar injection of bimatoprost is tolerated without immediate adverse effects in mice. Our results suggest a potential future application of prostaglandin analogues in the treatment of TAO.
KW - Adipogenesis
KW - Bimatoprost
KW - Brown adipose tissue
KW - Prostaglandins
KW - Thyroid eye disease
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U2 - 10.1167/iovs.18-25134
DO - 10.1167/iovs.18-25134
M3 - Article
C2 - 30551199
AN - SCOPUS:85058906851
VL - 59
SP - 5912
EP - 5923
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 15
ER -