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Editors Selection IGR 12-4
Basic Research: Model for glucocorticoid-induced glaucoma
Comment by John Danias on:
48130 Perfusion-cultured bovine anterior segments as an ex vivo model for studying glucocorticoid-induced ocular hypertension and glaucoma, Mao W; Tovar-Vidales T; Yorio T et al., Investigative Ophthalmology and Visual Science, 2011; 52: 8068-8075
Mao et al. (1955) describe a new ex-vivo model of steroid-induced glaucoma. The authors created a custom perfusion apparatus for perfusing bovine anterior segments obtained from the local abattoir. Using this apparatus they were able to determine a baseline outflow facility for these isolated segments. When exposed to dexamethasone in the perfusate, approximately 40% of the tested anterior segments showed a decrease in outflow facility that was more than two standard deviations away from the mean facility at baseline. The authors further determined that myocilin upregulation only occurred in the anterior segments that exhibited a significant change in outflow facility. Interestingly such a commitant change was not observed in the levels of fibronectin (another gene that is known to be changing after treatment with steroids). Anterior segments were perfused for a maximum of eight days. The work described in this paper is very important. The authors have come up with an ingenious system that can circumvent the problems of cost and availability associated with using human anterior segments for perfusion.
Perfusion of bovine anterior segments is an ingenious system that can circumvent the problems of cost and availability associated with using human anterior segments for perfusion
Although bovine eyes are not identical to primate ones, their physiology and anatomy in terms of outflow is reasonably close (and in any case much closer than that of primates and rabbits). Bovine eyes can be maintained for sufficiently long periods in perfusion to allow collection of meaningful data.
The authors correctly point out differences of the perfusion model they created with in-vivo model of steroid induced glaucoma in cows that have been previously described. They point out that the difference in the steroid response rate between these two models may be attributable to the particular breed of the cows used. However, the two models are not necessarily comparable in that respect. In the in-vivo model, IOP elevation occurs after four weeks of treatment while in the in-vitro model outflow facility change occurs within a few days in the eyes that respond.
The underlying assumption in this work is that flow in the cow eye is five ul/min and that needs to be verified experimentally in the future. A different flow rate for example will undoubtedly affect the cutoff point for decrease outflow facility determination. More importantly, since the authors used single-rate perfusion (rather than the traditional two-level) for outflow facility determination, there may be some errors in the values of outflow facility for some of the eyes. Notwithstanding this issue, this is an important piece of experimental work that increases the toolset we can use to understand steroidinduced and other open-angle glaucomas.
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