Impact of Lacrimal Gland Extraction on the Contralateral Eye in an Animal Model for Dry Eye Disease
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: Although there is still no consensus on the best animal model for dry eye disease research, a model based on lacrimalgland extraction (LGE) model is widely used. In this study, we aimed to investigate the histopathological changes takingplace on the contralateral eye after unilateral LGE to determine whether it is useful as a control. Methods: Seven-week-old male C57BL/6 mice were divided into naive control, environmental chamber model, and LGEgroups. Corneal fluorescein staining was scored to quantify the severity of damage. Morphological changes in the cornea,conjunctiva, and lacrimal gland (LG) were determined by hematoxylin and eosin staining and compared to those on naive controlanimals. Results: Compared to naive subjects, the unilateral LGE model showed enhanced corneal erosion scores and loss of conjunctivalgoblet cells, not only on the ipsilateral but also on the contralateral side. These changes in the ocular surface becamemore pronounced in a time-dependent manner. Furthermore, loss of LG acinar cells and leukocyte infiltration were detectedin the contralateral LGs of the LGE model. Conclusions: Considering the changes observed in the ocular surface and LGs, the contralateral side of the LGE model maynot offer proper control conditions for the experimental comparison of the effects of dry eye disease in vivo. There may beregulatory feedback or crosstalk system between both eyes activated in response to LGE.
Abstract
Purpose: Although there is still no consensus on the best animal model for dry eye disease research, a model based on lacrimalgland extraction (LGE) model is widely used. In this study, we aimed to investigate the histopathological changes takingplace on the contralateral eye after unilateral LGE to determine whether it is useful as a control. Methods: Seven-week-old male C57BL/6 mice were divided into naive control, environmental chamber model, and LGEgroups. Corneal fluorescein staining was scored to quantify the severity of damage. Morphological changes in the cornea,conjunctiva, and lacrimal gland (LG) were determined by hematoxylin and eosin staining and compared to those on naive controlanimals. Results: Compared to naive subjects, the unilateral LGE model showed enhanced corneal erosion scores and loss of conjunctivalgoblet cells, not only on the ipsilateral but also on the contralateral side. These changes in the ocular surface becamemore pronounced in a time-dependent manner. Furthermore, loss of LG acinar cells and leukocyte infiltration were detectedin the contralateral LGs of the LGE model. Conclusions: Considering the changes observed in the ocular surface and LGs, the contralateral side of the LGE model maynot offer proper control conditions for the experimental comparison of the effects of dry eye disease in vivo. There may beregulatory feedback or crosstalk system between both eyes activated in response to LGE.
참고문헌 (38)
- Hantera MM, "Trends in dry eye disease management worldwide", Clin Ophthalmol, 15, pp.165~173 (2021)
- Alkabbani S, "The prevalence, severity, and risk factors for dry eye disease in Dubai: a cross sectional study", BMC Ophthalmol, 21, pp.219~ (2021)
- Shanti Y, "Prevalence and associated risk factors of dry eye disease in 16 northern West bank towns in Palestine : a cross-sectional study", BMC Ophthalmol, 20, pp.26~ (2020)
- Ji YW, "Lacrimal gland-derived IL-22 regulates IL-17-mediated ocular mucosal inflammation", Mucosal Immunol, 10, pp.1202~1210 (2017)
- Lee HK, "Bilateral effect of the unilateral corneal nerve cut on both ocular surface and lacrimal gland", Invest Ophthalmol Vis Sci, 60, pp.430~441 (2019)
- Ji YW, "HIF1α-mediated TRAIL expression regulates lacrimal gland inflammation in dry eye disease", Invest Ophthalmol Vis Sci, 61, pp.3~ (2020)
- Zoukhri D, "Effect of inflammation on lacrimal gland function", Exp Eye Res, 82, pp.885~898 (2006)
- Schrader S, "Animal models of dry eye", Dev Ophthalmol, 41, pp.298~312 (2008)
- Bron AJ, "Diagnosis of dry eye", Surv Ophthalmol, 45(Suppl 2), pp.S221~S226 (2001)
- Stern ME, "What we have learned from animal models of dry eye", Int Ophthalmol Clin, 57, pp.109~118 (2017)
- Lio CT, "Cluster a nalysis of dry eye disease models based on immune cell parameters : new insight into therapeutic perspective", Front Immunol, 11, pp.1930~ (2020)
- Willcox M, "TFOS DEWS II tear film report", Ocul Surf, 15, pp.366~403 (2017)
- Bron AJ, "TFOS DEWS II pathophysiology report", Ocul Surf, 15, pp.438~510 (2017)
- Novack GD, "TFOS DEWS II clinical trial design report", Ocul Surf, 15, pp.629~649 (2017)
- Eom Y, "Meibomian glands and ocular surface changes after closure of meibomian gland orifices in rabbits", Cornea, 37, pp.218~226 (2018)
- Xiao B, "Dynamic ocular surface and lacrimal gland changes induced in experimental murine dry eye", PLoS One, 10, pp.e0115333~ (2015)
- Kong L, "Inappropriate apoptosis of salivary and lacrimal gland epithelium of immunodeficient NOD-scid mice", Clin Exp Rheumatol, 16, pp.675~681 (1998)
- Seo Y, "Activation of HIF-1α(hypoxia inducible factor-1α)prevents dry eye-induced acinar cell death in the lacrimal gland", Cell Death Dis, 5, pp.e1309~ (2014)
- Ji YW, "The dopaminergic neuronal system regulates the inflammatory status of mouse lacrimal glands in dry eye disease", Invest Ophthalmol Vis Sci, 62, pp.14~ (2021)
- Li Z, "Effectiveness of topical infliximab in a mouse model of experimental dry eye", Cornea, 31(Suppl 1), pp.S25~S31 (2012)
- De Paiva CS, "Dry eye-induced conjunctival epithelial squamous metaplasia is modulated by interferon-gamma", Invest Ophthalmol Vis Sci, 48, pp.2553~2560 (2007)
- Ikeda K, "The effects of 3% diquafosol sodium eye drop application on meibomian gland and ocular surface alterations in the Cu, Zn-superoxide dismutase-1 (Sod1) knockout mice", Graefes Arch Clin Exp Ophthalmol, 256, pp.739~750 (2018)
- de Paiva CS, "Effects of aging in dry eye", Int Ophthalmol Clin, 57, pp.47~64 (2017)
- McClellan AJ, "Ocular surface disease and dacryoadenitis in aging C57BL", 6 mice, 2014, pp.184, 631~643
- Chang YA, "Animal models of dry eye : their strengths and limitations for studying human dry eye disease", J Chin Med Assoc, 84, pp.459~464 (2021)
- Maitchouk DY, "Tear production after unilateral removal of the main lacrimal gland in squirrel monkeys", Arch Ophthalmol, 118, pp.246~252 (2000)
- Muller LJ, "Corneal nerves: structure, contents and function", Exp Eye Res, 76, pp.521~542 (2003)
- Tuominen IS, "Corneal innervation and morphology in primary Sjögren’s syndrome", Invest Ophthalmol Vis Sci, 44, pp.2545~2549 (2003)
- Roda M, "Dry eye disease and tear cytokine levels : a meta-analysis", Int J Mol Sci, 21, pp.3111~ (2020)
- Belmonte C, "Neural basis of sensation in intact and injured corneas", Exp Eye Res, 78, pp.513~525 (2004)
- Sibony PA, "Vasoactive intestinal polypeptide and the innervation of the human lacrimal gland", Arch Ophthalmol, 106, pp.1085~1088 (1988)
- Dartt DA, "Regulation of tear secretion", Adv Exp Med Biol, 350, pp.1~9 (1994)
- Dartt DA, "Neural regulation of lacrimal gland secretory processes : relevance in dry eye diseases", Prog Retin Eye Res, 28, pp.155~177 (2009)
- Botelho SY, "Functional innervation of the lacrimal gland in the cat. Origin of secretomotor fibers in the lacrimal nerve", Arch Ophthalmol, 76, pp.581~588 (1966)
- Botelho SY, "Tears and the lacrimal gland", Sci Am, 211, pp.78~86 (1964)
- Yamaguchi T, "Bilateral alterations in corneal nerves, dendritic cells, and tear cytokine levels in ocular surface disease", Cornea, 35(Suppl 1), pp.S65~S70 (2016)
- Liu X, "Bilateral limbal stem cell alterations in patients with unilateral herpes simplex keratitis and herpes zoster ophthalmicus as shown by in vivo confocal microscopy", Invest Ophthalmol Vis Sci, 62, pp.12~ (2021)
- Hamrah P, "Corneal sensation and subbasal nerve alterations in patients with herpes simplex keratitis : an in vivo confocal microscopy study", Ophthalmology, 117, pp.1930~1936 (2010)