Cited by 51Xenotransplantation and immune responseCorneal Surgery and TreatmentsTissue Engineering and Regenerative Medicine

Finding an Optimal Corneal Xenograft Using Comparative Analysis of Corneal Matrix Proteins Across Species

Open access
Sharifi, R., Yang, Y., Adibnia, Y., Dohlman, C. H., Chodosh, J., Gonzalez-Andrades, M.·2019·Scientific Reports

Abstract

Numerous animal species have been proposed as sources of corneal tissue for obtaining decellularized xenografts. The selection of an appropriate animal model must take into consideration the differences in the composition and structure of corneal proteins between humans and other animal species in order to minimize immune response and improve outcome of the xenotransplant. Here, we compared the amino-acid sequences of 16 proteins present in the corneal stromal matrix of 14 different animal species using Basic Local Alignment Search Tool, and calculated a similarity score compared to the respective human sequence. Primary amino acid structures, isoelectric point and grand average of hydropathy (GRAVY) values of the 7 most abundant proteins ( i.e . collagen α-1 (I), α-1 (VI), α-2 (I) and α-3 (VI), as well as decorin, lumican, and keratocan) were also extracted and compared to those of human. The pig had the highest similarity score (91.8%). All species showed a lower proline content compared to human. Isoelectric point of pig (7.1) was the closest to the human. Most species have higher GRAVY values compared to human except horse. Our results suggest that porcine cornea has a higher relative suitability for corneal transplantation into humans compared to other studied species.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41598-018-38342-4

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The application of many dECM scaffolds still encounters immunologic hurdles, hampering their translation into the clinic.

    “The application of many dECM scaffolds still encounters immunologic hurdles, hampering their translation into the clinic [33].”

    From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [33]

    The Introduction (page unavailable) says decellularization of xenogeneic corneas can leave antigenic components that still elicit an immune response. The Results and Discussion (page unavailable) likewise identifies antigenicity as an obstacle to successful corneal xenotransplantation. The paper supports the immunologic hurdle for xenogeneic corneal scaffolds, but does not establish the claim across many types of dECM scaffold or directly assess their clinical translation. (LLM, conf=0.84)

    Experimental — accuracy not yet measured
  • The application of dECM bioscaffolds still confronts major immunologic challenges.

    “However, the application of these bioscaffolds still confronts major immunologic challenges.”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 52

  1. [1]Gain P Global Survey of Corneal Transplantation and Eye Banking JAMA Ophthalmol 2016 134 167 173 10.1001/jamaophthalmol.2015.4776 26633035 · DOI
  2. [2]Pascolini D Mariotti SP Global estimates of visual impairment: 2010 Br J Ophthalmol 2012 96 614 618 10.1136/bjophthalmol-2011-300539 22133988 · DOI
  3. [3]Duan X McLaughlin C Griffith M Sheardown H Biofunctionalization of collagen for improved biological response: scaffolds for corneal tissue engineering Biomaterials 2007 28 78 88 10.1016/j.biomaterials.2006.08.034 16962168 · DOI
  4. [4]Gonzalez-Andrades M Improving the practicality and safety of artificial corneas: Pre-assembly and gamma-rays sterilization of the boston keratoprosthesis Ocul Surf 2018 10.1016/j.jtos.2018.04.002 29627599 · DOI
  5. [5]Islam, M. M. et al. Biomaterials-enabled cornea regeneration in patients at high risk for rejection of donor tissue transplantation. Npj Regen Med3, 10.1038/s41536-017-0038-8 (2018). PMC5792605 29423280 · DOI
  6. [6]Fagerholm, P. et al. A Biosynthetic Alternative to Human Donor Tissue for Inducing CornealRegeneration: 24-Month Follow-Up of a Phase 1 Clinical Study. Science Translational Medicine2, 10.1126/scitranslmed.3001022 (2010). 20739681 · DOI · Paper page
  7. [7]Gonzalez-Andrades M Generation of bioengineered corneas with decellularized xenografts and human keratocytes Invest Ophthalmol Vis Sci 2011 52 215 222 10.1167/iovs.09-4773 20739475 · DOI
  8. [8]Lynch AP Ahearne M Strategies for developing decellularized corneal scaffolds Exp Eye Res 2013 108 42 47 10.1016/j.exer.2012.12.012 23287438 · DOI
  9. [9]Leijten J Spatially and temporally controlled hydrogels for tissue engineering Mat Sci Eng R 2017 119 1 35 10.1016/j.mser.2017.07.001 PMC5708586 29200661 · DOI
  10. [10]Badylak SF Decellularized Allogeneic and Xenogeneic Tissue as a Bioscaffold for Regenerative Medicine: Factors that Influence the Host Response Ann Biomed Eng 2014 42 1517 1527 10.1007/s10439-013-0963-7 24402648 · DOI · Paper page
  11. [12]Schenke-Layland K Impact of decellularization of xenogeneic tissue on extracellular matrix integrity for tissue engineering of heart valves J Struct Biol 2003 143 201 208 10.1016/j.jsb.2003.08.002 14572475 · DOI · Paper page
  12. [14]Lawson JH Platt JL Molecular barriers to xenotransplantation Transplantation 1996 62 303 310 10.1097/00007890-199608150-00001 8779674 · DOI
  13. [15]Hara H Cooper DK The immunology of corneal xenotransplantation: a review of the literature Xenotransplantation 2010 17 338 349 10.1111/j.1399-3089.2010.00608.x 20955291 · DOI
  14. [16]Hara H In vitro investigation of pig cells for resistance to human antibody-mediated rejection Transpl Int 2008 21 1163 1174 10.1111/j.1432-2277.2008.00736.x 18764834 · DOI
  15. [18]Crapo PM Gilbert TW Badylak SF An overview of tissue and whole organ decellularization processes Biomaterials 2011 32 3233 3243 10.1016/j.biomaterials.2011.01.057 21296410 PMC3084613 · DOI · Paper page
  16. [19]Badylak SF Xenogeneic extracellular matrix as a scaffold for tissue reconstruction Transpl Immunol 2004 12 367 377 10.1016/j.trim.2003.12.016 15157928 · DOI · Paper page
  17. [20]Badylak SF Taylor D Uygun K Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds Annu Rev Biomed Eng 2011 13 27 53 10.1146/annurev-bioeng-071910-124743 21417722 PMC10887492 · DOI · Paper page
  18. [21]Wilson SL Sidney LE Dunphy SE Dua HS Hopkinson A Corneal Decellularization: A Method of Recycling Unsuitable Donor Tissue for Clinical Translation? Curr Eye Res 2016 41 769 782 10.3109/02713683.2015.1062114 26397030 PMC4926783 · DOI · Paper page
  19. [22]Wang Y Determinants of antigenicity and specificity in immune response for protein sequences BMC Bioinformatics 2011 12 251 10.1186/1471-2105-12-251 21693021 PMC3133554 · DOI
  20. [23]Hara H Cooper DK Xenotransplantation–the future of corneal transplantation? Cornea 2011 30 371 378 10.1097/ICO.0b013e3181f237ef 21099407 PMC3081421 · DOI
  21. [24]Levy MF Animal organs for human transplantation: how close are we? Proceedings (Baylor University Medical Center) 2000 13 3 6 PMC1312205 16389317
  22. [25]Dyrlund TF Human cornea proteome: identification and quantitation of the proteins of the three main layers including epithelium, stroma, and endothelium J Proteome Res 2012 11 4231 4239 10.1021/pr300358k 22698189 PMC3411198 · DOI
  23. [26]Lynn AK Yannas IV Bonfield W Antigenicity and immunogenicity of collagen J Biomed Mater Res B Appl Biomater 2004 71 343 354 10.1002/jbm.b.30096 15386396 · DOI
  24. [27]Cooper DK Gollackner B Sachs DH Will the pig solve the transplantation backlog? Annu Rev Med 2002 53 133 147 10.1146/annurev.med.53.082901.103900 11818467 · DOI
  25. [28]Taniguchi S Cooper DK Clinical xenotransplantation: past, present and future Ann R Coll Surg Engl 1997 79 13 19 9038490 PMC2502626
  26. [29]Manji RA Lee W Cooper DKC Xenograft bioprosthetic heart valves: Past, present and future Int J Surg 2015 23 280 284 10.1016/j.ijsu.2015.07.009 26190838 · DOI
  27. [30]Lamm V Hara H Mammen A Dhaliwal D Cooper DK Corneal blindness and xenotransplantation Xenotransplantation 2014 21 99 114 10.1111/xen.12082 25268248 PMC4181387 · DOI
  28. [31]Bueno JM Gualda EJ Artal P Analysis of corneal stroma organization with wavefront optimized nonlinear microscopy Cornea 2011 30 692 701 10.1097/ICO.0b013e3182000f94 21242785 · DOI
  29. [32]Mccormick CC Fullmer CS Garvey JS Amino-Acid Sequence and Comparative Antigenicity of Chicken Metallothionein Proceedings of the National Academy of Sciences of the United States of America 1988 85 309 313 10.1073/pnas.85.2.309 2448773 PMC279537 · DOI
  30. [33]Morishige N Takagi Y Chikama T-I Takahara A Nishida T Three-Dimensional Analysis of Collagen Lamellae in the Anterior Stroma of the Human Cornea Visualized by Second Harmonic Generation Imaging Microscopy Investigative Ophthalmology & Visual Science 2011 52 911 915 10.1167/iovs.10-5657 20881300 · DOI · Paper page
  31. [34]Winkler M Three-dimensional distribution of transverse collagen fibers in the anterior human corneal stroma Investigative ophthalmology & visual science 2013 54 7293 7301 10.1167/iovs.13-13150 24114547 PMC4589141 · DOI · Paper page
  32. [35]Winkler M A Comparative Study of Vertebrate Corneal Structure: The Evolution of a Refractive Lens Investigative ophthalmology & visual science 2015 56 2764 2772 10.1167/iovs.15-16584 26066606 PMC4416662 · DOI · Paper page
  33. [36]Abahussin M 3D Collagen Orientation Study of the Human Cornea Using X-ray Diffraction and Femtosecond Laser Technology Investigative Ophthalmology & Visual Science 2009 50 5159 5164 10.1167/iovs.09-3669 19516010 · DOI · Paper page
  34. [38]Watanabe S Tsutsui J Electrophoretic study of corneal proteins. Comparative analysis of corneal protein fractions in different animal species Am J Ophthalmol 1961 51 314 319 10.1016/0002-9394(61)91954-7 13783343 · DOI
  35. [39]Chen J Liu H Yang J Chou KC Prediction of linear B-cell epitopes using amino acid pair antigenicity scale Amino Acids 2007 33 423 428 10.1007/s00726-006-0485-9 17252308 · DOI
  36. [40]Jespersen MC Peters B Nielsen M Marcatili P BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes Nucleic Acids Res 2017 45 W24 W29 10.1093/nar/gkx346 28472356 PMC5570230 · DOI
  37. [41]Hofmann HJ Hadge D On the Theoretical Prediction of Protein Antigenic Determinants from Amino-Acid Sequences Biomed Biochim Acta 1987 46 855 866 2451516
  38. [42]Altschul SF Gish W Miller W Myers EW Lipman DJ Basic local alignment search tool J Mol Biol 1990 215 403 410 10.1016/S0022-2836(05)80360-2 2231712 · DOI · Paper page
  39. [43]Mount, D. W. Using the Basic Local Alignment Search Tool (BLAST). CSH Protoc 2007, pdbtop17, 10.1101/pdb.top17 (2007). 21357135 · DOI
  40. [44]Hinchliff CE Synthesis of phylogeny and taxonomy into a comprehensive tree of life Proceedings of the National Academy of Sciences 2015 112 12764 10.1073/pnas.1423041112 PMC4611642 26385966 · DOI
  41. [45]Jonasova K Kozmik Z Eye evolution: Lens and cornea as an upgrade of animal visual system Semin Cell Dev Biol 2008 19 71 81 10.1016/j.semcdb.2007.10.005 18035562 · DOI
  42. [46]Tomii K Sawada Y Honda S Convergent evolution in structural elements of proteins investigated using cross profile analysis BMC Bioinformatics 2012 13 11 10.1186/1471-2105-13-11 22244085 PMC3398312 · DOI
  43. [47]Suzuki Y Predictability of antigenic evolution for H3N2 human influenza A virus Genes Genet Syst 2013 88 225 232 10.1266/ggs.88.225 24463525 · DOI
  44. [48]Hopp TP Woods KR Prediction of protein antigenic determinants from amino acid sequences Proc Natl Acad Sci USA 1981 78 3824 3828 10.1073/pnas.78.6.3824 6167991 PMC319665 · DOI
  45. [49]Michelacci YM Collagens and proteoglycans of the corneal extracellular matrix Braz J Med Biol Res 2003 36 1037 1046 10.1590/S0100-879X2003000800009 12886457 · DOI
  46. [50]Quantock AJ Meek KM Chakravarti S An x-ray diffraction investigation of corneal structure in lumican-deficient mice Invest Ophthalmol Vis Sci 2001 42 1750 1756 11431438
  47. [51]Lewis D Ultrastructural localization of sulfated and unsulfated keratan sulfate in normal and macular corneal dystrophy type I Glycobiology 2000 10 305 312 10.1093/glycob/10.3.305 10704529 · DOI
  48. [52]Kim YG Identification of alpha-Gal and non-Gal epitopes in pig corneal endothelial cells and keratocytes by using mass spectrometry Curr Eye Res 2009 34 877 895 10.3109/02713680903184243 19895316 · DOI
  49. [53]Lee W Expression of NeuGc on Pig Corneas and Its Potential Significance in Pig Corneal Xenotransplantation Cornea 2016 35 105 113 10.1097/ICO.0000000000000635 26418433 PMC4847538 · DOI
  50. [54]Choi HJ Blockade of CD40-CD154 costimulatory pathway promotes long-term survival of full-thickness porcine corneal grafts in nonhuman primates: clinically applicable xenocorneal transplantation Am J Transplant 2015 15 628 641 10.1111/ajt.13057 25676390 · DOI
  51. [55]Lee HI Gal alpha(1-3)Gal expression of the cornea in vitro, in vivo and in xenotransplantation Xenotransplantation 2007 14 612 618 10.1111/j.1399-3089.2007.00433.x 17991149 · DOI
  52. [56]NCBI. Protein, https://www.ncbi.nlm.nih.gov/protein (2018).

Cited by

Sorted by citations

Authors
Sharifi, R., Yang, Y., Adibnia, Y., Dohlman, C. H., Chodosh, J., & Gonzalez-Andrades, M.
Affiliations
  • Massachusetts Eye and Ear Infirmary (US)
  • Yeditepe University (TR)
Venue
Scientific Reports
Published
2019-02-12
Volume
9
Issue
1
Pages
1876-1876
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2921956590
Cited by
51
References
4
Citations by year
2026: 8 · 2025: 5 · 2024: 9 · 2023: 6 · 2022: 4 · 2021: 8 · 2020: 8 · 2019: 2
FWCI
5.26
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RISalud Institutional Health Repository of Andalucía (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Corneal Surgery and Treatments
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
porcine cornea, species selection, amino acid sequence similarity, decorin, lumican, keratocan, isoelectric point, GRAVY, proline content, xenotransplantation, corneal transplantation
MeSH terms
Lumican, Algorithms, Animals, Collagen, Extracellular Matrix, Eye Proteins, Horses, Humans, Isoelectric Point, Neoplasm Transplantation, Phylogeny, Proline, Proteoglycans, Species Specificity, Swine, Transplantation, Heterologous, Corneal Transplantation, Sequence Alignment, Computational Biology, Decorin, Heterografts

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review