A method for registration of toxic drug effects on corneal endothelium

Abstract

A weight recording system (Medin & Davanger 1988, 1989), was used to demonstrate possible toxic damage of a medicament to the endothelium of rabbit corneas stored in organ culture. Seven corneas were stored in organ culture medium containing gentamicin (3.0 mg/ml). Seven other corneas stored in identical organ culture medium without gentamicin served as controls. The corneas were followed with weight recordings for up to 76 h. A toxic effect of gentamicin was demonstrated by a rapid weight increase in the corneas stored in the presence of gentamicin. After 5.3 h there was a significant difference (P = 0.0002) between the average weights of the two groups, and this difference increased during the following 2-3 days. Corneas from the two groups were also examined by light microscopy and scanning electron microscopy. There was good accordance between the weight recordings and the morphology. The weight recording system detects clearly the toxic effect of gentamicin (3.0 mg/ml).

Further evaluation of a method used for investigation of toxic drug effects

“…The standard deviation (SD) was less than 1%, and there was no significant difference between series performed by two different recorders. The reproducibility of the test was focused upon by calculating the SD of the control group, and by comparing the present results with the results of a control group in a recently published study (Medin 1992). The SD was approximately 2.8%, and no significant difference was found.…”

“…Corneas from young adult rabbits were trephined under sterile conditions and further prepared as described in a recent paper (Medin 1992). They were suspended in an organ culture medium (RPMI 1640 with Hepes buffer, at 34°C) and their weights were recorded.…”

“…They were suspended in an organ culture medium (RPMI 1640 with Hepes buffer, at 34°C) and their weights were recorded. Before further treatment they were all kept in the culture medium for 24 h to gain some weight stabilization (Medin 1992).…”

“…To examine the reproducibility of the test the weight increase of the control corneas was compared with the weight increase from 24 h to 48 h of the control corneas in a recently published paper (Medin 1992 c.kntmydn-mehnl-" I Fig. 1.…”

“…In a recent study gentamicin was added to the medium of organ cultured rabbit corneas, to a final concentration of 3 mg/ml (Medin 1992). This drug concentration produced toxic damage to the endothelium, and this was observed by SEM (scanning electron microscopy) and light microscopy.…”