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The survival and rejection of epithelium in experimental corneal ...

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178 Khodadoust <strong>and</strong> Silverste<strong>in</strong> Investigative Ophthalmology<br />

April 1969<br />

<strong>in</strong>filtrate, <strong>in</strong> front <strong>of</strong> which lies apparently<br />

normal donor <strong>epithelium</strong>, <strong>and</strong> beh<strong>in</strong>d<br />

which is found a th<strong>in</strong> layer <strong>of</strong> recipient<br />

<strong>epithelium</strong> slid<strong>in</strong>g <strong>in</strong> to heal the defect.<br />

Most significant <strong>in</strong> the present discussion<br />

is the fact that whenever this epithelial<br />

<strong>rejection</strong> commences, even 6 months after<br />

transplantation, it always starts precisely<br />

at the marg<strong>in</strong> <strong>of</strong> the graft, <strong>in</strong>dicat<strong>in</strong>g quite<br />

clearly that there has been no substitution<br />

<strong>of</strong> host for donor epithelial cells across the<br />

graft border.<br />

<strong>The</strong> characteristic migrat<strong>in</strong>g epithelial<br />

l<strong>in</strong>e described is considered to be a specific<br />

allograft <strong>rejection</strong> reaction to donor<br />

<strong>epithelium</strong> based upon the follow<strong>in</strong>g observations<br />

:<br />

1. It occurs only on allografts when the<br />

donor <strong>epithelium</strong> is <strong>in</strong>tact; on no occasion<br />

was a similar phenomenon seen <strong>in</strong>volv<strong>in</strong>g<br />

autograft <strong>epithelium</strong>, or on the surface <strong>of</strong><br />

allografts when the donor <strong>epithelium</strong> was<br />

removed prior to transplantation <strong>and</strong> permitted<br />

to be replaced by recipient <strong>epithelium</strong>.<br />

2. It is not a nonspecific response to the<br />

<strong>rejection</strong> <strong>of</strong> underly<strong>in</strong>g stroma, s<strong>in</strong>ce it has<br />

been observed to precede, to follow, or to<br />

progress <strong>in</strong> concert with the <strong>rejection</strong> <strong>of</strong><br />

stroma. Furthermore, <strong>rejection</strong> <strong>of</strong> the pure<br />

stromal allograft covered by host <strong>epithelium</strong><br />

is unaccompanied by a similar epithelial<br />

defect. F<strong>in</strong>ally, prelim<strong>in</strong>ary work<br />

with pure epithelial allografts ls <strong>in</strong>dicates<br />

that donor epithelial <strong>rejection</strong> may take<br />

place over the surface <strong>of</strong> the host's own<br />

stroma <strong>and</strong> endothelium.<br />

3. <strong>The</strong> start<strong>in</strong>g po<strong>in</strong>t, extension, <strong>and</strong><br />

direction <strong>of</strong> migration <strong>of</strong> the epithelial <strong>rejection</strong><br />

l<strong>in</strong>e are <strong>in</strong>variably related closely<br />

to the extent <strong>and</strong> distribution <strong>of</strong> <strong>corneal</strong><br />

vascularization near the graft marg<strong>in</strong>, <strong>and</strong><br />

the mov<strong>in</strong>g epithelial defect is never seen<br />

to extend beyond the boundary <strong>of</strong> the<br />

donor graft onto host cornea.<br />

4. In the mildly vascularized lamellar<br />

graft <strong>in</strong> which <strong>rejection</strong> does not occur<br />

spontaneously, epithelial <strong>rejection</strong> may be<br />

<strong>in</strong>duced by orthotopic sk<strong>in</strong> transplantation<br />

only from the same donor which provided<br />

the <strong>corneal</strong> graft.<br />

5. In the heavily vascularized lamellar<br />

allograft, the m<strong>in</strong>imal time <strong>of</strong> epithelial<br />

<strong>rejection</strong> (14 days) is the same as that<br />

observed by Bill<strong>in</strong>gham <strong>and</strong> Boswell 19 <strong>in</strong><br />

their study <strong>of</strong> the <strong>rejection</strong> <strong>of</strong> <strong>corneal</strong> grafts<br />

transplanted ectopically onto a vascularized<br />

bed formed on the sk<strong>in</strong>. Moreover, the <strong>rejection</strong><br />

<strong>of</strong> <strong>epithelium</strong> on the <strong>corneal</strong> graft<br />

has been found to be accompanied by sensitization<br />

<strong>of</strong> the host, as evidenced by second-set<br />

<strong>rejection</strong> <strong>of</strong> a sk<strong>in</strong> graft from the<br />

same donor.<br />

We wish to express our appreciation for the<br />

competent technical assistance <strong>of</strong> Mahmood Farazdaghi.<br />

REFERENCES<br />

1. Basu, P. K., Miller, I., <strong>and</strong> Ormsby, H. L.:<br />

Sex chromat<strong>in</strong> as a biologic cell marker <strong>in</strong> the<br />

study <strong>of</strong> the fate <strong>of</strong> <strong>corneal</strong> transplants, Am.<br />

J. Ophth. 49: 513, 1960.<br />

2. Hanna, C, <strong>and</strong> Irw<strong>in</strong>, E. S.: Fate <strong>of</strong> cells<br />

<strong>in</strong> the <strong>corneal</strong> graft, Arch. Ophth. 63: 810,<br />

1962.<br />

3. Polack, F. M., Smelser, G. K., <strong>and</strong> Rose, J.:<br />

Long-term <strong>survival</strong> <strong>of</strong> isotopically labeled<br />

stromal <strong>and</strong> endothelial cells <strong>in</strong> <strong>corneal</strong> homografts,<br />

Am. J. Ophth. 57: 67, 1964.<br />

4. Chi, H. H., Teng, C. C, <strong>and</strong> Katz<strong>in</strong>, H. M.:<br />

<strong>The</strong> fate <strong>of</strong> endothelial cells <strong>in</strong> <strong>corneal</strong> homografts,<br />

Am. J. Ophth. 59: 186, 1965.<br />

5. Khodadoust, A. A.: Lamellar <strong>corneal</strong> transplantation<br />

<strong>in</strong> the rabbit, Am. J. Ophth. 66:<br />

1111, 1968.<br />

6. Khodadoust, A. A.: Penetrat<strong>in</strong>g <strong>corneal</strong> transplantation<br />

<strong>in</strong> the rabbit, Am. J. Ophth. 66:<br />

899, 1968.<br />

7. Khodadoust, A. A., Silverste<strong>in</strong>, A. M., <strong>and</strong><br />

Maumenee, A. E.: Allograft <strong>rejection</strong> <strong>of</strong> <strong>experimental</strong><br />

lamellar <strong>corneal</strong> transplants. In<br />

preparation.<br />

8. Khodadoust, A. A., Silverste<strong>in</strong>, A. M., <strong>and</strong><br />

Maumenee, A. E.: Allograft <strong>rejection</strong> <strong>of</strong> <strong>experimental</strong><br />

penetrat<strong>in</strong>g <strong>corneal</strong> transplants.<br />

In preparation.<br />

9. Polack, F. M., <strong>and</strong> Smelser, G. K.: <strong>The</strong> persistence<br />

<strong>of</strong> isotopically labeled cells <strong>in</strong> <strong>corneal</strong><br />

grafts, Proc. Soc. Exper. Biol. & Med. 110:<br />

60, 1962.<br />

10. Hanna, C, <strong>and</strong> O'Brien, J. E.: Cell production<br />

<strong>and</strong> migration <strong>in</strong> the epithelial layer <strong>of</strong><br />

the cornea, Arch. Ophth. 64: 536, 1960.<br />

11. Bonnefon, G., <strong>and</strong> Lacoste, A.: Recherches

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