Abstract
Ocular IgE-associated allergy ranges from mild disease (seasonal and perennial allergic conjunctivitis) to more chronic/severe and vision-threatening forms (atopic and vernal keratoconjunctivitis). Whereas mild forms of disease have been studied extensively, less is known about the more chronic forms. Our lab has helped to address this knowledge gap by developing and characterizing an allergen-induced, chronic/severe, IgE-associated model of ocular allergy referred to as the severe allergic eye disease (AED) model. It is distinct from previously described models that mimic the more mild forms, referred to in the literature as the allergic conjunctivitis (AC) model. The purpose of this method article is to detail the protocol to induce and characterize the AED model and directly compare these mice to the mild AC model. Troubleshooting and implications are also discussed.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Groneberg DA, Bielory L, Fischer A, Bonini S, Wahn U (2003) Animal models of allergic and inflammatory conjunctivitis. Allergy 58(11):1101–1113
Magone MT, Chan CC, Rizzo LV, Kozhich AT, Whitcup SM (1998) A novel murine model of allergic conjunctivitis. Clin Immunol Immunopathol 87(1):75–84
Reyes NJ, Saban DR (2014) T helper subsets in allergic eye disease. Curr Opin Allergy Clin Immunol 14(5):477–484. https://doi.org/10.1097/ACI.0000000000000088
Stern ME, Siemasko K, Gao J, Duong A, Beauregard C, Calder V, Niederkorn JY (2005) Role of interferon-gamma in a mouse model of allergic conjunctivitis. Invest Ophthalmol Vis Sci 46(9):3239–3246. https://doi.org/10.1167/iovs.05-0138
Ono SJ, Abelson MB (2005) Allergic conjunctivitis: update on pathophysiology and prospects for future treatment. J Allergy Clin Immunol 115(1):118–122. https://doi.org/10.1016/j.jaci.2004.10.042
Calder VL, Jolly G, Hingorani M, Adamson P, Leonardi A, Secchi AG, Buckley RJ, Lightman S (1999) Cytokine production and mRNA expression by conjunctival T-cell lines in chronic allergic eye disease. Clin Exp Allergy 29(9):1214–1222
Chiaramonte MG, Donaldson DD, Cheever AW, Wynn TA (1999) An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response. J Clin Invest 104(6):777–785. https://doi.org/10.1172/JCI7325
Lee CG, Homer RJ, Zhu Z, Lanone S, Wang X, Koteliansky V, Shipley JM, Gotwals P, Noble P, Chen Q, Senior RM, Elias JA (2001) Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta(1). J Exp Med 194(6):809–821
Leonardi A, Cortivo R, Fregona I, Plebani M, Secchi AG, Abatangelo G (2003) Effects of Th2 cytokines on expression of collagen, MMP-1, and TIMP-1 in conjunctival fibroblasts. Invest Ophthalmol Vis Sci 44(1):183–189
Saw VP, Offiah I, Dart RJ, Galatowicz G, Dart JK, Daniels JT, Calder VL (2009) Conjunctival interleukin-13 expression in mucous membrane pemphigoid and functional effects of interleukin-13 on conjunctival fibroblasts in vitro. Am J Pathol 175(6):2406–2415. https://doi.org/10.2353/ajpath.2009.090579
Zicari AM, Nebbioso M, Zicari A, Mari E, Celani C, Occasi F, Tubili F, Duse M (2013) Serum levels of IL-17 in patients with vernal keratoconjunctivitis: a preliminary report. Eur Rev Med Pharmacol Sci 17(9):1242–1244
Saban DR (2014) The chemokine receptor CCR7 expressed by dendritic cells: a key player in corneal and ocular surface inflammation. Ocul Surf 12(2):87–99. https://doi.org/10.1016/j.jtos.2013.10.007
Chen JJ, Applebaum DS, Sun GS, Pflugfelder SC (2013) Atopic keratoconjunctivitis: a review. J Am Acad Dermatol 70(3):569–575. https://doi.org/10.1016/j.jaad.2013.10.036
Foulks GN, Nichols KK, Bron AJ, Holland EJ, McDonald MB, Nelson JD (2012) Improving awareness, identification, and management of meibomian gland dysfunction. Ophthalmology 119(10 Suppl):S1–S12. https://doi.org/10.1016/j.ophtha.2012.06.064
Knop E, Knop N, Millar T, Obata H, Sullivan DA (2011) The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Invest Ophthalmol Vis Sci 52(4):1938–1978. https://doi.org/10.1167/iovs.10-6997c
Ahadome SD, Mathew R, Reyes NJ, Mettu PS, Cousins SW, Calder VL, Saban DR (2016) Classical dendritic cells mediate fibrosis directly via the retinoic acid pathway in severe eye allergy. JCI Insight 1(12):e87012. https://doi.org/10.1172/jci.insight.87012
Leonardi A, Jose PJ, Zhan H, Calder VL (2003) Tear and mucus eotaxin-1 and eotaxin-2 in allergic keratoconjunctivitis. Ophthalmology 110(3):487–492. https://doi.org/10.1016/S0161-6420(02)01767-0
Reyes NJ, Blanco-Mezquita T, Mathew R, Saban D (2014) Novel mouse model of severe ocular allergy reveals a key role for pathogenic Th17 cells. Invest Ophthalmol Vis Sci 55(E-Abstract):4058
Lee HS, Hos D, Blanco T, Bock F, Reyes NJ, Mathew R, Cursiefen C, Dana R, Saban DR (2015) Involvement of corneal lymphangiogenesis in a mouse model of allergic eye disease. Invest Ophthalmol Vis Sci 56(5):3140–3148. https://doi.org/10.1167/iovs.14-16186
Lee HS, Schlereth S, Khandelwal P, Saban DR (2013) Ocular allergy modulation to hi-dose antigen sensitization is a Treg-dependent process. PLoS One 8(9):e75769. https://doi.org/10.1371/journal.pone.0075769
Reyes NJ, Mayhew E, Chen PW, Niederkorn JY (2010) NKT cells are necessary for maximal expression of allergic conjunctivitis. Int Immunol 22(8):627–636. https://doi.org/10.1093/intimm/dxq046
Khandelwal P, Blanco-Mezquita T, Emami P, Lee HS, Reyes NJ, Mathew R, Huang R, Saban DR (2013) Ocular mucosal CD11b+ and CD103+ mouse dendritic cells under normal conditions and in allergic immune responses. PLoS One 8(5):e64193. https://doi.org/10.1371/journal.pone.0064193
Schlereth S, Lee HS, Khandelwal P, Saban DR (2012) Blocking CCR7 at the ocular surface impairs the pathogenic contribution of dendritic cells in allergic conjunctivitis. Am J Pathol 180(6):2351–2360. https://doi.org/10.1016/j.ajpath.2012.02.015
Acknowledgments
This work was supported by NIH grant R01EY021798 (Saban), P30EY005722 (Saban), F32EY025557 (Reyes), and P31 Core Grant.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Reyes, N.J., Mathew, R., Saban, D.R. (2018). Induction and Characterization of the Allergic Eye Disease Mouse Model. In: Reinhardt, R. (eds) Type 2 Immunity. Methods in Molecular Biology, vol 1799. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-7896-0_5
Download citation
DOI: https://doi.org/10.1007/978-1-4939-7896-0_5
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-4939-7895-3
Online ISBN: 978-1-4939-7896-0
eBook Packages: Springer Protocols