Skip to main content

The Use of Animal Models to Assess Engineered Corneal Tissue

  • Protocol
  • First Online:
Corneal Regeneration

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2145))

Abstract

Tissue-engineered corneal constructs offer the potential of readily available corneal substitutes for transplantation. As with all medical devices and implants, these constructs require rigorous safety assessments, combined with well-described analyses of the implant’s physical and biological characteristics. Although the constructs are developed in vitro, such studies are currently unable to fully emulate the complex biomechanical and biochemical conditions within living tissue, as well as the interplay between this environment and immunological factors. For these reasons, animal models remain essential to characterize such interactions. They form a stage where corneal implants can be tested for utility and survival in a living location to assess their ability to provide vision and avoid adverse event. Here, we examine the surgical considerations of animal models and we describe how the rabbit can be used for this purpose. This animal has been the routine model for ophthalmological studies and we set out methods to implant corneal constructs with this species.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 149.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Russell WMS, Burch RL (1959) The principles of humane experimental technique. Methuen, London

    Google Scholar 

  2. Council directive 2010/63/eu on the protection of animals used for scientific purposes (2010) vol L276. European Parliament

    Google Scholar 

  3. Council NR (2011) Guide for the care and use of laboratory animals, 8th edn. The National Academies Press, Washington, DC

    Google Scholar 

  4. Arvo statement for the use of animals in ophthalmology and vision research (2016) The Association for Research in Vision and Ophthalmology. https://www.arvo.org/About/policies/statement-for-the-use-of-animals-in-ophthalmic-and-vision-research/

  5. Zernii EY, Baksheeva VE, Iomdina EN, Averina OA, Permyakov SE, Philippov PP, Zamyatnin AA, Senin II (2016) Rabbit models of ocular diseases: new relevance for classical approaches. CNS Neurol Disord Drug Targets 15(3):267–291. https://doi.org/10.2174/1871527315666151110124957

    Article  CAS  PubMed  Google Scholar 

  6. Murphy KL, Roughan JV, Baxter MG, Flecknell PA (2010) Anaesthesia with a combination of ketamine and medetomidine in the rabbit: effect of premedication with buprenorphine. Vet Anaesth Analg 37(3):222–229. https://doi.org/10.1111/j.1467-2995.2009.00525.x. VAA525 [pii]

    Article  CAS  PubMed  Google Scholar 

  7. She SC, Steahly LP, Moticka EJ (1990) A method for performing full-thickness, orthotopic, penetrating keratoplasty in the mouse. Ophthalmic Surg 21(11):781–785

    CAS  PubMed  Google Scholar 

  8. Brunette I, Rosolen SG, Carrier M, Abderrahman M, Nada O, Germain L, Proulx S (2011) Comparison of the pig and feline models for full thickness corneal transplantation. Vet Ophthalmol 14(6):365–377. https://doi.org/10.1111/j.1463-5224.2011.00886.x

    Article  CAS  PubMed  Google Scholar 

  9. York M, Steiling W (1998) A critical review of the assessment of eye irritation potential using the Draize rabbit eye test. J Appl Toxicol 18(4):233–240. https://doi.org/10.1002/(sici)1099-1263(199807/08)18:4<233::aid-jat496>3.0.co;2-y

    Article  CAS  PubMed  Google Scholar 

  10. Thomasy SM, Eaton JS, Timberlake MJ, Miller PE, Matsumoto S, Murphy CJ (2016) Species differences in the geometry of the anterior segment differentially affect anterior chamber cell scoring systems in laboratory animals. J Ocul Pharmacol Ther 32(1):28–37. https://doi.org/10.1089/jop.2015.0071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Olsen EG, Davanger M (1984) The healing of rabbit corneal endothelium. Acta Ophthalmol (Copenh) 62(5):796–807. https://doi.org/10.1111/j.1755-3768.1984.tb05808.x

    Article  CAS  Google Scholar 

  12. Gwon A (2008) The rabbit in cataract/IOL surgery. In: Tsonis PA (ed) Animal models in eye research. Academic Press, London, pp 184–204. https://doi.org/10.1016/B978-0-12-374169-1.00013-8

    Chapter  Google Scholar 

  13. Wenger S, Müllhaupt D, Ohlerth S, Prasse S, Klein K, da Silva VB, Mosing M (2017) Experimental evaluation of four airway devices in anaesthetized new zealand white rabbits. Vet Anaesth Analg 44(3):529–537. https://doi.org/10.1016/j.vaa.2016.05.009

    Article  PubMed  Google Scholar 

  14. Holve DL, Mundwiler KE, Pritt SL (2011) Incidence of spontaneous ocular lesions in laboratory rabbits. Comp Med 61(5):436–440

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Botha GS (1958) Histological observations on the gastro-esophageal junction in the rabbit. J Anat 92(3):441–446

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Flecknell PA, Roughan JV, Hedenqvist P (1999) Induction of anaesthesia with sevoflurane and isoflurane in the rabbit. Lab Anim 33(1):41–46. https://doi.org/10.1258/002367799780578516

    Article  CAS  PubMed  Google Scholar 

  17. Aguayo Bonniard A, Yeung JY, Chan CC, Birt CM (2016) Ocular surface toxicity from glaucoma topical medications and associated preservatives such as benzalkonium chloride (bak). Expert Opin Drug Metab Toxicol 12(11):1279–1289. https://doi.org/10.1080/17425255.2016.1209481

    Article  CAS  PubMed  Google Scholar 

  18. Lee S, Khun D, Kumarasinghe GL, De Zoysa GH, Sarojini V, Vellara HR, Rupenthal ID, Thakur SS (2019) Ex vivo evaluation of the stability, safety and antibacterial efficacy of an extemporaneous povidone-iodine preparation for ophthalmic applications. Clin Exp Optom. https://doi.org/10.1111/cxo.12899

  19. Larry AM, Nemiroff B, John LU, Hf E, Charlesworth LD (1987) Role of the rabbit nictitating membrane in ocular irritancy testing. J Toxicol Cutan Ocul Toxicol 6(1):43–56. https://doi.org/10.3109/15569528709052164

    Article  Google Scholar 

  20. Wilson G, O'Leary DJ, Vaughan W (1984) Differential swelling in compartments of the corneal stroma. Invest Ophthalmol Vis Sci 25(9):1105–1108

    CAS  PubMed  Google Scholar 

  21. Cain W Jr, Sinskey RM (1981) Detection of anterior chamber leakage with seidel’s test. Arch Ophthalmol 99(11):2013. https://doi.org/10.1001/archopht.1981.03930020889015

    Article  PubMed  Google Scholar 

  22. Koch JM, Refojo MF, Leong FL, Kenyon KR (1989) Keratopathy of the rabbit cornea following complete eyelid closure. Acta Ophthalmol Suppl 192:108–114

    CAS  PubMed  Google Scholar 

  23. Keating SC, Thomas AA, Flecknell PA, Leach MC (2012) Evaluation of emla cream for preventing pain during tattooing of rabbits: changes in physiological, behavioural and facial expression responses. PLoS One 7(9):e44437. https://doi.org/10.1371/journal.pone.0044437. PONE-D-12-17063 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter W. Madden .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Brady, R.T., Madden, P.W. (2020). The Use of Animal Models to Assess Engineered Corneal Tissue. In: Ahearne, M. (eds) Corneal Regeneration. Methods in Molecular Biology, vol 2145. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0599-8_15

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-0599-8_15

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0598-1

  • Online ISBN: 978-1-0716-0599-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics