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Yelin Yang, Roholah Sharifi, Adibnia Yashar, Miguel Gonzalez-Andrades; Finding An Optimal Corneal Xenograft: Comparative Analysis Of Corneal Matrix Proteins Across Species. . Invest. Ophthalmol. Vis. Sci. 2018;59(9):1409.
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© ARVO (1962-2015); The Authors (2016-present)
The shortage of donor corneas worldwide has led to an increased interest in xenotransplantation. Animal tissues often contain antigenic elements that can be recognized as foreign by the host tissue, and consequently leads to an immune-mediated rejection. The dissimilarity of protein composition between donor and host tissues is one of the most important elements of such antigenicity and can greatly affect the ultimate outcome. Thus, it is crucial to use species with the corneal stromal protein composition that is most similar to humans in order to minimize the host immune response. We aim to investigate the differences in corneal matrix proteins between various animal species, and compare to human.
Species that were most commonly used for studies in clinical applications of corneal transplant were included in the study: pig, rabbit, guinea pig, chick, cat, dog, rat, mice, bovine, sheep, goat, horse, and zebrafish. From literature review, we identified 18 most abundant proteins present in the corneal stroma including collagens, proteoglycans (decorin, lumican, keratocan, biglycan), MAM domain containing protein 2 (MAMDC2), prolargin and vimentin. The corresponding protein for each species was obtained through PUBMED protein database. The protein for each species was compared to human using BLAST (Basic Search Alignment Search Tool). A final weighted score of corneal stromal protein compared to human was calculated based on reported abundance of these proteins.
Primary sequence analysis of proteins has demonstrated that pig cornea has the highest resemblance to humans in 4 of 8 of the collagens examined. Moreover, proteoglycan compositions of cat and horse cornea were the most similar to humans, while chick and zebrafish were the least similar. Most of the species had comparable sequences of MAMDC2, prolargin and vimentin, with the exception of chick and zebrafish. Finally, pig had the highest score (93% resemblance compared to human), while zebrafish, horse and chick had the lowest scores (72%, 84% and 85% respectively). The other species fell within a close range.
Overall, the protein composition of the extracellular matrix of the corneal stroma of pig was the most similar compared to human. Selection of the right animal model may help to reduce antigenicity and improve outcomes of corneal xenografts.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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