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01-01-2021 | Original Paper

Intrastromal implantation of chicken corneal grafts into the cornea of rabbits for corneal thickening: an experimental study

Authors: Flavia Motta Almodin, Juliana Motta Almodin, Edna Motta Almodin, Nilma Fernandes, Paulo Ferrara, Antonio Gonçalves

Published in: International Ophthalmology | Issue 1/2021

Abstract

Purpose

To evaluate the feasibility and effects of the intrastromal implantation of chemically modified corneal stroma obtained from chicken into the corneas of rabbits for corneal thickening.

Methods

Chicken corneas were cut, debrided, treated with cross-linking and implanted in an intrastromal pouch created in the cornea of 10 white New Zealand rabbits with femtosecond laser. Slit-lamp biomicroscopy and optical coherence tomography were performed immediately, 7, 30 and 90 days postoperatively. Corneas were removed at 90 days and cut in two halves. One half was sent to histological analysis for the presence of necrosis, polymorphonuclear inflammatory cells, blood vessels and fibrosis, while the other half was evaluated with transmission electron microscopy to verify tissue organization and the presence of keratocytes and inflammatory cells. Corneal thicknesses were comparatively analyzed over time with Wilcoxon test (p ≤ 0.05).

Results

The chicken grafts were incorporated into the cornea of all animals over time. Mean rabbit cornea thickness increased from 338 µm preoperatively to 538 µm (p < 0.0077) at 90 days, while mean chicken graft thickness decreased from 350 to 215 µm (p < 0.0077). No clear signs of rejection attributable to the xenograft were observed in any of the implanted eyes. However, some macroscopic and histological events were observed in some of the eyes, probably due to procedural issues during implantation.

Conclusion

The intrastromal implantation of chicken grafts was shown to be feasible and predictable to thicken the recipient rabbit cornea without apparent rejection. However, before being considered in humans, further meticulous clinical trials are required to establish the clinical utility, safety and efficacy of xenografts for the treatment of patients with advanced keratoconus.

Rabinowitz YS (1998) Keratoconus. Surv Ophthalmol 42:297–319. https://doi.org/10.1016/s0039-6257(97)00119-7CrossRefPubMed

Hamdi IM (2011) Preliminary results of intrastromal corneal ring segments implantation to treat moderate to severe keratoconus. J Cataract Refract Surg 37:1125–1132. https://doi.org/10.1016/j.jcrs.2010.12.048CrossRefPubMed

Ashwin PT, McDonnell PJ (2010) Collagen cross-linkage: a comprehensive review and directions for future research. Br J Ophthalmol 94:965–970. https://doi.org/10.1136/bjo.2009.164228CrossRefPubMed

Jhanji V, Sharma N, Vajpayee RB (2010) Management of keratoconus: current scenario. Br J Ophthalmol 95:1044–1050. https://doi.org/10.1136/bjo.2010.185868CrossRefPubMed

Tan DT, Dart JK, Holland EJ, Kinoshita S (2012) Corneal transplantation. Lancet 379:1749–1761. https://doi.org/10.1016/S0140-6736(12)60437-1CrossRefPubMed

Kelly TL, Williams KA, Coster DJ (2011) Australian corneal graft registry. Corneal transplant for keratoconus: a registry study. Arch Ophthalmol 129:691–697. https://doi.org/10.1001/archophthalmol.2011.7CrossRefPubMed

Kremer I, Eagle RC, Rapuano CJ, Laibson PR (1995) Histologic evidence of recurrent keratoconus seven years after keratoplasty. Am J Ophthalmol 119:511–512. https://doi.org/10.1016/s0002-9394(14)71239-5CrossRefPubMed

Tuft SJ, Buckley RJ (1995) Iris ischaemia following penetrating keratoplasty for keratoconus (Urrets-Zavalia syndrome). Cornea 14(6):618–622PubMed

Liu H, Zhu W, Jiang AC, Sprecher AJ, Zhou X (2012) Femtosecond laser lenticule transplant in rabbit cornea: experimental study. J Refract Surg 28:907–911. https://doi.org/10.3928/1081597X-20121115-05CrossRefPubMed

10.

Liu R, Zhao J, Xu Y, Li M, Niu L, Liu H, Sun L, Chu R, Zhou X (2015) Femtosecond laser-assisted corneal small incision allogeneic intrastromal lenticule implantation in monkeys: a pilot study. Invest Ophthalmol Vis Sci 56:3715–3720. https://doi.org/10.1167/iovs.14-15296CrossRefPubMed

11.

Zhao J, Shen Y, Tian M, Sun L, Zhao Y, Zhang X, Zhou X (2017) Corneal lenticule allotransplant after femtosecond laser small incision lenticule extraction in rabbits. Cornea 36(2):222–228. https://doi.org/10.1097/ICO.0000000000001076CrossRefPubMed

12.

Sekundo W, Kunert K, Russmann C, Gille A, Bissmann W, Stobrawa G, Sticker M, Bischoff M, Blum M (2008) First efficacy and safety study of femtosecond lenticule extraction for the correction of myopia: six-month results. J Cataract Refract Surg 34:1513–1520. https://doi.org/10.1016/j.jcrs.2008.05.033CrossRefPubMed

13.

van Dijk K, Liarakos VS, Parker J, Ham L, Lie JT, Groeneveld-van Beek EA, Melles GR (2015) Bowman layer transplant to reduce and stabilize progressive, advanced keratoconus. Ophthalmology 122:909–917. https://doi.org/10.1016/j.ophtha.2014.12.005CrossRefPubMed

14.

Li M, Li M, Sun L, Han T, Ding L, Xiang J, Zhou X (2018) In vivo confocal microscopic investigation of the cornea after autologous implantation of lenticules obtained through small incision lenticule extraction for treatment of hyperopia. Clin Exp Optom 101:38–45. https://doi.org/10.1111/cxo.12595CrossRefPubMed

15.

Almodin EM, Ferrara P, Camin FMA, Colallilo JMA (2018) Femtosecond laser–assisted intrastromal corneal lenticule implantation for treatment of advanced keratoconus in a child’s eye. J Cataract Refract Surg 6:25–29. https://doi.org/10.1016/j.jcro.2018.01.004CrossRef

16.

Pascolini D, Mariotti SP (2010) Global estimates of visual impairment. Br J Ophthalmol 96:614–618. https://doi.org/10.1136/bjophthalmol-2011-300539CrossRef

17.

Alió Del Barrio JL, El Zarif M, de Miguel MP, Azaar A, Makdissy N, Harb W, El Achkar I, Arnalich-Montiel F, Alió JL (2017) Cellular therapy with human autologous adipose-derived adult stem cells for advanced keratoconus. Cornea 36:952–960. https://doi.org/10.1097/ICO.0000000000001228CrossRefPubMed

18.

Gonzalez-Andrades M, Sharifi R, Islam MM, Divoux T, Haist M, Paschalis EI, Gelfand L, Mamodaly S, Di Cecilia L, Cruzat A, Ulm FJ, Chodosh J, Delori F, Dohlman CH (2018) Improving the practicality and safety of artificial corneas: pre-assembly and gamma-rays sterilization of the Boston Keratoprosthesis. Ocul Surf 16:322–330. https://doi.org/10.1016/j.jtos.2018.04.002CrossRefPubMed

19.

Islam MM, Buznyk O, Reddy JC, Pasyechnikova N, Alarcon EI, Hayes S, Lewis P, Fagerholm P, He C, Iakymenko S, Liu W, Meek KM, Sangwan VS, Griffith M (2018) Biomaterials-enabled cornea regeneration in patients at high risk for rejection of donor tissue transplantation. NPJ Regen Me 3:2. https://doi.org/10.1038/s41536-017-0038-8CrossRef

20.

Isaacson A, Swioklo S, Connon CJ (2018) 3D bioprinting of a corneal stroma equivalent. Exp Eye Res 173:188–193. https://doi.org/10.1016/j.exer.2018.05.010CrossRefPubMedPubMedCentral

21.

Zhang B, Xue Q, Li J, Ma L, Yao Y, Ye H, Cui Z, Yang H (2019) 3D bioprinting for artificial cornea: Challenges and perspectives. Med Eng Phys 71:68–78. https://doi.org/10.1016/j.medengphy.2019.05.002CrossRefPubMed

22.

Jin H, Liu L, Ding H, He M, Zhang C, Zhong X (2018) Small incision femtosecond laser-assisted x-ray-irradiated corneal intrastromal xenotransplantation in rhesus monkeys: a preliminary study. Curr Mol Med 18:612–621. https://doi.org/10.2174/1566524019666190129123935CrossRefPubMedPubMedCentral

23.

Zheng X, Zhang D, Li S, Zhang J, Zheng J, Du L, Gao J (2018) An experimental study of femto-laser in assisting xenograft acellular cornea matrix lens transplantation. Med Sci Monit 27(24):5208–5215. https://doi.org/10.12659/MSM.909294CrossRef

24.

Schenke-Layland K et al (2003) Impact of decellularization of xenogeneic tissue on extracellular matrix integrity for tissue engineering of heart valves. J Struct Biol 143:201–208. https://doi.org/10.1016/j.jsb.2003.08.002CrossRefPubMed

25.

Fowler WC, Chang DH, Roberts BC, Zarovnaya EL, Proia AD (2004) A new paradigm for corneal wound healing research: the white leghorn chicken (Gallus gallus domesticus). Curr Eye Res 28:241–250. https://doi.org/10.1076/ceyr.28.4.241.27837CrossRefPubMed

26.

Almodin CG, Minguetti-Camara VC, Meister H, Ferreira JO, Franco RL, Cavalcante AA, Radaelli MR, Bahls AS, Moron AF, Murta CG (2004) Recovery of fertility after grafting of cryopreserved germinative tissue in female rabbits following radiotherapy. Hum Reprod 19:1287–1293. https://doi.org/10.1093/humrep/deh246CrossRefPubMed

27.

Cerialle PMA, Almodin CG, Radaelli MRM, Minguetti-Câmara VC, Souza MC, Oliveira CAM, Gonçalves AJ (2017) Viability of homologous and heterologous subcutaneous transplant of fresh germ cells in rabbits. JBRA Assist Reprod 21:73–78. https://doi.org/10.5935/1518-0557.20170019CrossRefPubMedPubMedCentral

28.

Bromley JG, Randleman JB (2010) Treatment strategies for corneal ectasia. Curr Opin Ophthalmol 21:255–258. https://doi.org/10.1097/ICU.0b013e32833a8bfeCrossRefPubMedPubMedCentral

29.

Akhtar S, Bron AJ, Salvi SM, Hawksworth NR, Tuft SJ, Meek KM (2008) Ultrastructural analysis of collagen fibrils and proteoglycans in keratoconus. Acta Ophthalmol 86:764–772. https://doi.org/10.1111/j.1755-3768.2007.01142.xCrossRefPubMed

30.

Suwan-Apichon O, Reyes JM, Griffin NB, Barker J, Gore P, Chuck RS (2006) Microkeratome versus femtosecond laser predissection of corneal grafts for anterior and posterior lamellar keratoplasty. Cornea 25:966–968. https://doi.org/10.1097/01.ico.0000226360.34301.29CrossRefPubMed

31.

Mian SI, Shtein RM (2007) Femtosecond laser-assisted corneal surgery. Curr Opin Ophthalmol 18:295–299. https://doi.org/10.1097/ICU.0b013e3281a4776cCrossRefPubMed

32.

Shousha MA, Yoo SH, Kymionis GD, Ide T, Feuer W, Karp CL, O'Brien TP, Culbertson WW, Alfonso E (2011) Long-term results of femtosecond laser-assisted sutureless anterior lamellar keratoplasty. Ophthalmology 118:315–323. https://doi.org/10.1016/j.ophtha.2010.06.037CrossRefPubMed

33.

del Barrio JLA, Chiesa M, Garagorri N, Garcia-Urquia N, Fernandez-Delgado J, Bataille L, Rodriguez A, Arnalich-Montiel F, Zarnowski T, de Toledo JPÁ, Alio JL, De Miguel MP (2015) Acellular human corneal matrix sheets seeded with human adipose-derived mesenchymal stem cells integrate functionally in an experimental animal model. Exp Eye Res 132:91–100. https://doi.org/10.1016/j.exer.2015.01.020CrossRef

34.

Cissell DD, Hu JC, Griffiths LG, Athanasiou KA (2014) Antigen removal for the production of biomechanically functional, xenogeneic tissue grafts. J Biomech 47:1987–1996. https://doi.org/10.1016/j.jbiomech.2013.10.041CrossRefPubMed

35.

Sharifi R, Yang Y, Adibnia Y, Dohlman CH, Chodosh J, Gonzalez-Andrades M (2019) Finding an optimal corneal xenograft using comparative analysis of corneal matrix proteins across species. Sci Rep 9:19876. https://doi.org/10.1038/s41598-018-38342-4CrossRef

36.

Li A, Zhang Y, Liu Y, Pan Z (2017) Corneal xenotransplantation from pig to rhesus monkey: no signs of transmission of endogenous porcine retroviruses. Transplant Proc 49:2209–2214. https://doi.org/10.1016/j.transproceed.2017.07.018CrossRefPubMed

37.

Badylak SF (2014) Decellularized allogeneic and xenogeneic tissue as a bioscaffold for regenerative medicine: factors that influence the host response. Ann Biomed Eng 42:1517–1527. https://doi.org/10.1007/s10439-013-0963-7CrossRefPubMed

38.

Isidan A, Liu S, Li P, Lashmet M, Smith LJ, Hara H, Cooper DKC, Ekser B (2019) Decellularization methods for developing porcine corneal xenografts and future perspectives. Xenotransplantation 28:e12564. https://doi.org/10.1111/xen.12564CrossRef

39.

Dana MR, Qian Y, Hamrah P (2000) Twenty-five-year panorama of corneal immunology: emerging concepts in the immunopathogenesis of microbial keratitis, peripheral ulcerative keratitis, and corneal transplant rejection. Cornea 19:625–643. https://doi.org/10.1097/00003226-200009000-00008CrossRefPubMed

40.

Maguire MG, Stark WJ, Gottsch JD, Stulting RD, Sugar A, Fink NE, Schwartz A (1994) Risk factors for corneal graft failure and rejection in the collaborative corneal transplant studies; Collaborative Corneal Transplant Studies Research Group. Ophthalmology 101:1536–1547. https://doi.org/10.1016/s0161-6420(94)31138-9CrossRefPubMed

41.

Qazi Y, Hamrah P (2013) Corneal allograft rejection: immunopathogenesis to therapeutics. J Clin Cell Immunol. https://doi.org/10.4172/2155-9899.S9-006CrossRefPubMedPubMedCentral

42.

Lindstrom RL, Macrae SM, Pepose JS, Hoopes PC Sr (2013) Corneal inlays for presbyopia correction. Curr Opin Ophthalmol 24:281–287. https://doi.org/10.1097/ICU.0b013e328362293eCrossRefPubMed

43.

Böhm M, Shajari M, Remy M, Kohnen T (2019) Corneal densitometry after accelerated corneal collagen cross-linking in progressive keratoconus. Int Ophthalmol 39:765–775. https://doi.org/10.1007/s10792-018-0876-4CrossRefPubMed

44.

Lopes B, Ramos I, Ambrósio R (2014) Corneal densitometry in keratoconus. Cornea 33:1282–1286. https://doi.org/10.1097/ICO.0000000000000266CrossRefPubMed

Title: Intrastromal implantation of chicken corneal grafts into the cornea of rabbits for corneal thickening: an experimental study
Authors: Flavia Motta Almodin
Juliana Motta Almodin
Edna Motta Almodin
Nilma Fernandes
Paulo Ferrara
Antonio Gonçalves
Publication date: 01-01-2021
Publisher: Springer Netherlands
Published in: International Ophthalmology / Issue 1/2021
Print ISSN: 0165-5701
Electronic ISSN: 1573-2630
DOI: https://doi.org/10.1007/s10792-020-01573-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Intrastromal implantation of chicken corneal grafts into the cornea of rabbits for corneal thickening: an experimental study

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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