Benzalkonium Chloride에 의한 각막내피세포 구조와 기능의 변화

Abstract

The purpose of this study was to evaluate alterations in corneal endothelial cell function and ultrastructure caused by benzalkonium chloride (BAC). Sixteen albino rabbits (32 eyes) were used for this study. One cornea of each matched pair was assigned to experimental group and the other cornea to control group. The experimental groups were divided into 4 groups, of which corneal endothelium were perfused with 0.01%, 0.001%, 0.0002%, and 0.0001% BAG. After paired rabbit corneas were isolated and mounted in the in vitro dual-chambered specular microscope, experimental corneas of each matched pair were perfused with different concentrations of BAC. Control corneas were perfused with glutathione-bicarbonate-Ringer solution (GBR). Corneal thickness was measured every 15 minutes throughout the perfusion period. Swelling rates were calculated by linear regression analysis, and compared to swelling rate of each paired mate perfused with GBR alone. At the end of perfusion, the corneas were fixed in 2.5% gluᅳ taraldehyde solution for transmission electron microscopy (TEM). Swelling rates of rabbit corneas perfused with BAC, 0.0001% did not differ significantly from control corneas (p>0.05). But, 0.0002%, 0.001%, and 0. 01% BAC differed significantly from control corneas (p<0.05). BAC, 0.0001% showed normal corneal endothelial findings, but 0.0002% and 0.001% BAC showed reversible endothelial cellular injury. BAC, 0.01% showed irreversible endothelial cellular injury such as loss of nuclear membrane and disruption of cellular organelles. The results of this study indicate that long-term use of topical eye solutions containing BAC might induce corneal endothelial damage, especially in the absence of epithelial barrier such as corneal ulcer.

Benzalkonium chloride(BAC)가 각막내피세포의 기능과 미세구조에 대한 영향올 알아보고 자 하였다. 백색가토 16마리를 대상으로 한눈은 실험군, 반대편 눈은 대조군으로 사용하였고 실험군은 다시 0.01%, 0.001%, 0.0002% 및 0.0001% BAC의 4군으로 나누었다. Dual-chambered specular microscope울 변형시킨 perfusion system에 가토의 각막을 고정하여 인공전방을 형성한 후 각 실험군의 각막내피세포는 해당농도의 BAC가 첨가된 glutathione-bicarbonate Ringer (GBR) 용액을, 대조군에는 GBR 용액만을 관류하였다. 관류하는 동안 매 15분마다 각막두께를 측정하여 시간에 따른 각막두께의 변화(각막부종률)를 비교 분석하였다. 관류실험후 각막은 투과전자현미경 관찰을 위해 2. 5% glutaraldehyde용액에 고정하였다. 0.0001% BAC군의 각막부종률은 대조군과 차이가 없었으나(p>0.05) 0.0002%, 0.001%, 0.01%에서는 각막부종률이 대조군에 비하여 현저하게 증가하였다(p<0.05). 전자현미경검사상 0.0001% BAC군에서는 정상적인 각막내피세포 소견을 보였으나，0.0002% BAC군과 0.001% BAC군에서는 가역적인 세포손상의 소견이 나타났고 0.01% BAC군에는 핵막이 소실 되고 세포내소기관이 파괴되는 비가역적 세포손상이 일어났다. 그러므로 장기간 BAC를 포함한 점안약을 점안할 때에, 특히 각막상피의 장벽기능이 없는 각막궤양둥의 질환시에는 주의가 필요 할 것으로 사료된다.