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Noriko Koizumi, Naoki Okumura, Yuji Sakamoto, Kenta Yamasaki, Makiko Nakahara, Ryuzo Torii, Morio Ueno, Junji Hamuro, Shigeru Kinoshita; Cell-injection Therapy using Cultivated Human Corneal Endothelial Cells in a Primate Model. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1738.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the feasibility of corneal endothelial reconstruction by a cell-injection therapy using cultivated human corneal endothelial cells (HCECs) in a non-human primate model.
Monkey corneal endothelium was intensively scraped off up to the peripheral area to make a corneal endothelial dysfunction model. A 2.0 x 105 amount of cultivated HCECs (passage 3) suspended in OptiMEM-I supplemented with 100μM of selective rho kinase (ROCK)-inhibitor Y-27632 was injected into the anterior chamber of 2 eyes of 2 animals (Y-27632(+) group). The same procedure was performed without using ROCK-inhibitor Y-27632 in 2 eyes of 2 animals (Y-27632(-) group). The eyes of each animal were then kept in the face-down position for 3 hours. In the control group, endothelial cells were scraped and HCECs were not injected (2 eyes). Slit-lamp examinations and corneal thickness- and intraocular pressure measurements were then performed for up to 2.5 months, followed by immunohistochemical analysis.
Two eyes in the control group demonstrated severe corneal edema and did not recover corneal clarity. In contrast, the 4 eyes that received cell-injection therapy showed improved corneal clarity. Corneal clarity recovered faster and the corneal thickness at 2.5 months after treatment was thinner in the Y-27632(+) eyes compared to the Y-27632(-) eyes (507μm and 961μm, respectively). A homogeneous monolayer of polygonal cells expressing ZO-1 and Na+/K+-ATPase was reconstructed in the Y-27632(+) group, and the corneal endothelial cell density was much higher in the Y-27632(+) group compared to the Y-27632(-) group. None of the eyes showed intraocular pressure elevation or an immunological rejection.
The findings of this present study indicate that cell-injection therapy using ROCK-inhibitor Y-27632 might be a clinically applicable procedure for corneal endothelial dysfunction.
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