토끼 모델에서 실험적 건성안 유도를 위한 염화벤잘코늄 농도 비교
Benzalkonium Chloride for Experimental Dry Eye Induction in a Rabbit Model
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목적: 본 연구는 토끼 모델에서 0.05%, 0.1%, 0.2% 농도의 염화벤잘코늄(benzalkonium chloride, BAC) 점안액이 임상인자 및 조직학적소견에 미치는 영향에 대해 비교 분석하고자 하였다. 대상과 방법: 0.05%, 0.1%, 0.2% 농도의 BAC 실험군 및 대조군을 분류하였으며, 각 군당 3마리의 토끼를 사용하였다. 세 가지 농도의BAC를 양안에 1회 2 μL, 1일 2회 총 14일간 국소 점안하였다. 그리고 baseline, 3일, 5일, 7일, 10일, 14일째에 토끼의 양안에서 눈물량, 눈물막 파괴시간 및 각막 형광염색점수를 측정하고 기록하였다. 건성안 유발 후 14일째에 모든 토끼를 안락사시키고 안구 조직을적출한 후 결막 내 술잔세포 농도 및 각막 상피 사멸세포수를 조사하였다. 결과: 0.05% BAC군은 14일째, 0.1% BAC군은 10일째, 0.2% BAC군은 실험 5일째 baseline에 비해 눈물 분비량 및 눈물막 파괴시간이감소하였고 각막 형광염색점수가 증가하였다(모두 p<0.05). 조직 검사 결과 대조군에 비하여 모든 실험군들의 결막 내 술잔세포수가감소하였으며 각막 사멸세포수는 증가하였다(모두 p<0.01). 특히, 결막 내 술잔세포수는 0.05% BAC군에 비해 0.2% BAC군에서 더낮았으며, 각막 상피 사멸세포수는 모든 실험군에서 각 군 간 차이를 보였다(모두 p<0.01). 결론: 0.2% BAC의 사용은 다른 농도의 BAC에 비해 초기에 임상적으로 의미가 있는 건성안 토끼 모델을 만들 수 있을 것으로 판단된다.
Abstract
Purpose: This study compared the clinical parameters and histological findings according to the benzalkonium chloride concentration (BAC; 0.05%, 0.1%, and 0.2%) for inducing experimental dry eye (EDE) in a rabbit model. Methods: Rabbits were divided into four groups according to the BAC concentration: untreated group, 0.05%, 0.1%, and 0.2% BAC. BAC was instilled topically in both eyes of the rabbits twice daily until they were euthanized after 14 days. Tear volume, tear break-up time (TBUT), and corneal fluorescein staining score (CFS) were measured 0, 3, 5, 7, and 14 days after treatment. After excising tissues on day 14, the conjunctival goblet cell density and corneal epithelial apoptosis were quantified. Results: The tear volume and TBUT were lower and the CFS was higher than baseline values after 14, 10, and 5 days in the 0.05, 0.1, and 0.2% BAC groups, respectively (all p < 0.05). At 14 days, the 0.2% BAC group showed more significant aggravation of all clinical parameters, and the 0.1% BAC group had a lower CFS (all p < 0.05) than the 0.05% BAC group. In all BAC groups, the conjunctival goblet cell density was lower and corneal epithelial apoptosis was significantly higher than in the untreated group (all p < 0.01). The conjunctival goblet cell density was lower in the 0.2% BAC group than in the 0.05% BAC group. Between-group differences in corneal epithelial apoptosis were observed in all experimental groups (all p < 0.01). Conclusions: Instilling BAC for 14 days induced EDE in the 0.05, 0.1, and 0.2% BAC groups. Although 0.2% BAC cannot be used for a severe EDE model, it is useful for inducing EDE in a rabbit model in a short time.
참고문헌 (17)
- Stapleton F, "TFOS DEWS II epidemiology report", Ocul Surf, 15, pp.334~365 (2017)
- Craig JP, "TFOS DEWS II definition and classification report", Ocul Surf, 15, pp.276~283 (2017)
- Willcox MDP, "TFOS DEWS II tear film report", Ocul Surf, 15, pp.366~403 (2017)
- Singh S, "Rabbit models of dry eye disease : current understanding and unmet needs for translational research", Exp Eye Res, 206, pp.108538~ (2021)
- Yoon KC, "Tear production and ocular surface changes in experimental dry eye after elimination of desiccating stress", Invest Ophthalmol Vis Sci, 52, pp.7267~7273 (2011)
- Yoon KC, "Expression of Th-1 chemokines and chemokine receptors on the ocular surface of C57BL", 6mice : effects of desiccating stress, 2007, pp.48, 2561~2569
- Chen XM, "A novel rabbit dry eye model induced by a controlled drying system", Transl Vis Sci Technol, 10, pp.32~ (2021)
- Lantyer-Araujo NL, "Rabbit as an animal model for ocular surface disease, tear osmolarity, electrolyte, and tear ferning profiles", Optom Vis Sci, 97, pp.847~851 (2020)
- Li N, "Establishment of the mild, moderate and severe dry eye models using three methods in rabbits", BMC Ophthalmol, 13, pp.50~ (2013)
- Li C, "Research on the stability of a rabbit dry eye model induced by topical application of the preservative benzalkonium chloride", PLoS One, 7, pp.e33688~ (2012)
- Carpena-Torres C, "Optimization of a rabbit dry eye model induced by topical instillation of benzalkonium chloride", J Ophthalmol, 2020, pp.7204951~ (2020)
- Xiong C, "A rabbit dry eye model induced by topical medication of a preservative benzalkonium chloride", Invest Ophthalmol Vis Sci, 49, pp.1850~1856 (2008)
- Chen X, "Toxicity of cosmetic preservatives on human ocular surface and adnexal cells", Exp Eye Res, 170, pp.188~197 (2018)
- Bron AJ, "TFOS DEWS II pathophysiology report", Ocul Surf, 15, pp.438~510 (2017)
- Uematsu M, "Acute corneal epithelial change after instillation of benzalkonium chloride evaluated using a newly developed in vivo corneal transepithelial electric resistance measurement method", Ophthalmic Res, 39, pp.308~314 (2007)
- Solomon A, "Pro-and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease", Invest Ophthalmol Vis Sci, 42, pp.2283~2292 (2001)
- De Saint Jean M, "Effects of benzalkonium chloride on growth and survival of Chang conjunctival cells", Invest Ophthalmol Vis Sci, 40, pp.619~630 (1999)