생쥐를 이용한 스테로이드 유발 고안압 모델
Steroid-Induced Ocular Hypertension Model in the Mice
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목적: 생쥐에서 스테로이드 점안이 고안압 녹내장 모델로서의 가능성이 있는지를 알아보기 위해 2개월간 스테로이드 점안 후 생쥐의안압과 망망신경절세포수 변화를 알아보았다. 대상과 방법: 생쥐에서 스테로이드 녹내장을 유발시키기 위해 덱사메타손 점안액을 하루 3회 4주간 점안하였다. 안압이 기저 안압 대비50% 이상 상승한 눈만을 대상으로 추가 4주간 하루 1회씩 점안을 하였다. 안압은 Rebound tonometry로 측정하였다. 8주 후 망막신경절세포의 선택적 면역형광염색과 전체 망막 층의 TUNEL 염색으로 실험군과 대조군 간의 변화를 관찰하였다. 결과: 실험군 20안 중 11안(55%)에서 덱사메타손 점안 4주째에 기저 안압 대비 50% 이상의 안압 상승을 보였다. 8주째 고안압군과대조군의 평균 안압은 각각 11.8 ± 1.4 mmHg와 18.5 ± 1.0 mmHg였다(p<0.01). 8주째 중심부의 망막신경절세포수는 각각 2,718± 240개와 2,612 ± 443개로 유의한 차이를 보이지 않았다(p=0.294). 두 군 간 TUNEL 양성 세포수의 차이도 나타나지 않았다. 그러나 아포프토시스와 관련된 Bax와 pBad의 발현은 실험군에서 증가하였다(p<0.05). 결론: 스테로이드 안약을 이용한 생쥐의 고안압 실험 모델은 쉽고 비교적 비침습적인 방법으로 국소적 합병증 없이 고안압을 유도하였다. 그러나 2개월간의 기저 안압 대비 50% 상승된 안압을 유지하는 것으로는 유의한 망막신경절세포수의 변화를 관찰할 수 없었으며,좀 더 장기적인 연구 결과와 전신 부작용에 대해서는 추가 연구가 필요할 것으로 생각한다.
Abstract
Purpose: To determine whether rat eyes develop increases in intraocular pressure (IOP) in response to a topically applied corticosteroidand to investigate the relationship between ocular hypertension and apoptosis of retinal ganglion cells. Methods: IOP was monitored by rebound tonometry in a group of 10 rats that received topically administered dexamethasone inboth eyes (experimental) and in another group of 5 rats that received artificial tears (control) three times daily for 4 weeks afterthe establishment of baseline IOP values. Only eyes that increased by more than 50% compared with the basal IOP were administeredonce per day for 5 weeks. After 8 weeks, selective immunofluorescence stain for retinal ganglion cells and terminaldeoxynucleotidyl transferase dUTP nick end labeling (TUNEL) stain were conducted. Results: Among 20 experimental eyes, 11 eyes (55%) showed a greater than 50% increase in IOP compared with basal IOP. After 8 weeks, the mean IOPs for the experimental and control groups were 11.8 ± 1.4 mm Hg and 18.5 ± 1.0 mm Hg, respectively(p < 0.01). The counts of central retinal ganglion cells (RGCs) were 2718 ± 240 and 2612 ± 443, respectively (p =0.294). The results of the TUNEL stain also showed no differences. Conclusions: Rat eyes exhibit a steroid-induced ocular hypertensive response with no local complications. However, maintainingocular hypertension increased by 50% for two months was not enough to detect changes in RGCs.
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