Abstract
In their article about the effect of intracameral injection of lidocaine and carbachol on the rabbit corneal endothelium, Liou and coauthors1 concluded that lidocaine 1% and carbachol 0.01% did not produce morphologic and functional changes in the corneal endothelial cells of rabbit. There are, however, a few issues worth discussing. First, the rabbit is undoubtedly the most commonly used animal model for studying drug toxicities on the corneal endothelium in vivo. However, this animal model has a major drawback. Unlike the corneal endothelial cells in humans, which have very limited regenerative capacity, corneal endothelial cells in rabbits regenerate rapidly and completely in response to minor to moderate injury.2 Second, it has been shown that a corneal endothelial injury may not become evident (even by very sensitive methods such as histology and terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling techniques) in the first few hours after injury,3 while the rabbit corneal thickness, which is a reflection of corneal endothelial function, may return to normal within a week.2 Therefore, the timing of serial investigatory measurements will be of utmost importance if one does not wish to miss the window period of endothelial cell injury. In Liou and coauthors' study,1 corneal endothelial cell count and corneal thickness were measured 2 hours, 1 week, and 1 month after the injection of drugs. Although all readings were within normal range, corneal endothelial injury, if present, could well be missed during the period between 2 hours and 1 week. Moreover, the alizarin red and trypan blue staining as well as scanning electron microscopy (SEM), which are much more sensitive than corneal thickness and cell count measurement in detecting endothelial cell injury, were done 1 month after the injection only. These investigations were unlikely to be revealing because the injured endothelial cells would have regenerated completely and could not be distinguished from noninjured cells at that time.2 If the rabbit is to be used as an animal model for testing drug toxicities in vivo, we would suggest at least 4 sets, if not more, of investigations be done—the first few hours, 1 to 2 days, 1 week, and 1 month after intracameral injection.4,5 Ideally, more sensitive investigatory methods such as histological staining and SEM would be used at each investigation. This may require sacrifice of animals with enucleation of their eyes for investigation at different stages throughout the experiment. Finally, we would like to commend the authors for their valuable work on this issue and hope that our suggestions will broaden the discussion. Alex H. Fan MBBS Arthur C.K. Cheng MRCSEd Srinivas K. Rao FRCSEd Li-Jia Chen Dennis S.C. Lam MD, FRCOphth Hong Kong, China
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