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KMID : 1813520190080020054
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Journal of the Korean Glaucoma Society
2019 Volume.8 No. 2 p.54 ~ p.62
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Wnt/β-catenin Signaling Pathway in a Rat Model of Ocular Hypertension: a Pilot Study
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Lee si-Hyung
Sim Kyeong-Sun
Kim Chan-Yun
Park Tae-Kwann
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Abstract
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Purpose : To investigate the involvement of Wnt/β-catenin signaling pathway in retinal ganglion cell (RGC) damage and aqueous humor outflow pathway in a rat model of ocular hypertension (OHT) using circumlimbal suture.
Methods : Fifteen Sprague Dawley rats were used for the experiment, and animals were divided into the non-OHT control (n = 5) and OHT group (n = 10). To produce OHT rat model, circumlimbal suture was performed in unilateral eyes of the rats, and intraocular pressure (IOP) was measured before and immediately after the procedure and daily until 1 week, and weekly until 1 months of the suture procedure. Animals were sacrified at 1 months of the surgery, and immunohistochemistry for β-catenin was conducted to examine the activation of Wnt/β-catenin signaling pathway in RGCs and anterior segment structure including TM and ciliary body. Quantitative reverse transcription polymerase chain reaction was performed to investigate the expression levels of various Wnt ligands, from Wnt1 to 10b.
Results : After the circumlimbal suture surgery, IOP was immediately elevated up to mid-fifties, and maintained at mid and high twenties until the animal sacrifice, while IOP level non-OHT control eyes were measured at between low to mid ten. Increased β-catenin expression was detected in RGCs of OHT eyes compared to control. β-catenin expression expression was also upregulated in trabecular meshwork, ciliary body, and iris of OHT eyes. For each Wnt ligands, Wnt3, Wnt3a, Wnt6, Wnt7a, and Wnt8a expression was upregulated in the retinas of OHT eyes, while Wnt5a and Wnt7a expression was increased in the anterior segment of OHT eyes.
Conclusions : Wnt/β-catenin signaling pathway was activated in both RGCs and TM of OHT eyes, and certain Wnt ligands were upregulated upon OHT insult. Further researches are needed to reveal the exact role of Wnt/β-catenin signaling pathway in RGCs and TM in glaucomatous animal models.
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KEYWORD
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Wnt/β-catenin signaling pathway, Ocular hypertension, Retinal ganglion cell, Trabecular meshwork
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