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Tomoka Uemura, Osamu Sakai, Yuji Sakamoto; Transgenic mice expressing Transforming growth factor-β2 increased intraocular pressure. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3773.
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Transforming growth factor-β (TGF-β) is the cytokine involved in various tissue growth and development. TGF-β2 is most abundant TGF-β isoform in the eye, and it is well known that the levels of TGF-β2 are elevated in the aqueous humor of primary open-angle glaucoma (POAG) patients. However, there are few report about the relationship between intraocular pressure (IOP) and TGF-β2 concentration in the aqueous humor in vivo. The purpose of this study is to examine the relationship of TGF-β2 on IOP using TGF-β2 transgenic mice.
TGF-β2 transgenic mice (active TGF-β2 over expressed under the lens specific promoter) were generated. The IOP measurement and slit lamp examination were performed at 4-16 week-old transgenic and wild type mice. The IOP was measured with TonoLab rebound tonometer under sevoflurane anesthesia. Mouse eye morphology at 16 week-old was evaluated by hematoxylin staining and total levels of TGF-β2 in aqueous humor at 16 week-old was detected by ELISA.
The IOP of TGF-β2 transgenic mice was significantly elevated versus wild type mice. The maximum IOP of TGF-β2 transgenic mice was 28.67±2.84 (average ± SEM) mmHg at 6 week-old, and IOP of wild type mice was 18.53±0.72 mmHg at the ages (P<0.01). The ocular hypertension lasted until approximately 12 week-old, but the IOP tended to decline after 13 week-old. Ciliary body hypoplasia, trabecular meshwork hypoplasia, and iridocorneal adhesion were observed in TGF-β2 transgenic mice. In addition, the number of retinal ganglion cells of TGF-β2 transgenic mice were reduced by around 60% of compared to those of wild type mice. Total TGFβ2 levels in aqueous humor of TGF-β2 transgenic mice (2.74±0.71 ng/mL) was significantly increased, compared to wild type mice (0.98±0.09 ng/mL). The TGF-β2 level in aqueous humor was significantly correlated with Maximum IOP (r = 0.80, P<0.01).
The huge amount of TGF-β2 consisted in aqueous humor of TGF-β2 transgenic mice, and led to change of the morphology of anterior chamber and increase of IOP. Our data suggest that TGF-β2 plays an important role in development of anterior chamber and ocular hypertension. This transgenic mice would be useful to study of morphology or investigate mechanism of increasing IOP.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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