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

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Volume 8<br />

Number 2<br />

Epithelium <strong>survival</strong> <strong>and</strong> <strong>rejection</strong> 175<br />

have <strong>in</strong>vaded from the limbus to the graft border.<br />

<strong>The</strong> epithelial <strong>rejection</strong> l<strong>in</strong>e is characterized histologically<br />

by a dense <strong>in</strong>filtrate <strong>of</strong> <strong>in</strong>flammatory cells<br />

<strong>and</strong> dead <strong>and</strong> dy<strong>in</strong>g <strong>epithelium</strong>; <strong>in</strong> front <strong>of</strong> this<br />

advanc<strong>in</strong>g l<strong>in</strong>e lies a normal thickness <strong>of</strong> healthy<br />

donor <strong>epithelium</strong>, while beh<strong>in</strong>d it is found a th<strong>in</strong><br />

layer <strong>of</strong> recipient <strong>epithelium</strong> rapidly slid<strong>in</strong>g <strong>in</strong> to<br />

heal the advanc<strong>in</strong>g defect. It was felt that the<br />

demonstration <strong>of</strong> the specific nature <strong>of</strong> this <strong>rejection</strong><br />

process, <strong>and</strong> the ability to elicit it long after<br />

the graft had been put <strong>in</strong>to place, would constitute<br />

the best pro<strong>of</strong> that allogeneic donor <strong>epithelium</strong><br />

can survive <strong>in</strong>def<strong>in</strong>itely on the recipient eye.<br />

<strong>The</strong> most efficient way to achieve sensitization<br />

by <strong>and</strong> <strong>rejection</strong> <strong>of</strong> the lamellar allograft is to<br />

stimulate vascular <strong>in</strong>growth from the limbus to the<br />

graft marg<strong>in</strong>. This may readily be accomplished<br />

by plac<strong>in</strong>g the graft eccentrically <strong>in</strong> the recipient<br />

cornea, with<strong>in</strong> a millimeter or two <strong>of</strong> the limbus.<br />

In this circumstance, that quadrant <strong>of</strong> the graft<br />

nearest the limbus becomes vascularized. In a<br />

series <strong>of</strong> 50 such eccentrically placed 8 mm. lamellar<br />

allografts performed <strong>in</strong> connection with<br />

this <strong>and</strong> another study, spontaneous <strong>rejection</strong> <strong>of</strong><br />

the graft was observed to start with<strong>in</strong> 2 to 6<br />

weeks after transplantation <strong>in</strong> 50 per cent <strong>of</strong> the<br />

cases. In most <strong>in</strong>stances, a discrete epithelial <strong>rejection</strong><br />

l<strong>in</strong>e was observed. Whether early or late<br />

after transplantation, the l<strong>in</strong>e <strong>in</strong>variably was first<br />

seen precisely at the graft marg<strong>in</strong> <strong>in</strong> apposition<br />

to the zone <strong>of</strong> vascularization. As the sta<strong>in</strong>able<br />

<strong>rejection</strong> l<strong>in</strong>e proceeded across the cornea <strong>in</strong> the<br />

direction <strong>of</strong> the avascular area (Fig. 4), it always<br />

extended as an arcuate l<strong>in</strong>e from one marg<strong>in</strong> <strong>of</strong><br />

the graft to the other <strong>and</strong> never <strong>in</strong>vaded the recipient<br />

cornea.<br />

Another way to <strong>in</strong>duce <strong>rejection</strong> <strong>of</strong> the lamellar<br />

allograft is to <strong>in</strong>cite vascular <strong>in</strong>growth toward a<br />

centrally placed graft by postpon<strong>in</strong>g removal <strong>of</strong><br />

the irritat<strong>in</strong>g sutures employed to fix the graft <strong>in</strong><br />

place. Should only a s<strong>in</strong>gle suture be left <strong>in</strong><br />

place, then frequently only one or a few capillary<br />

loops will grow <strong>in</strong> toward the graft marg<strong>in</strong>. We<br />

have observed <strong>in</strong> a number <strong>of</strong> such <strong>in</strong>stances the<br />

onset <strong>of</strong> graft <strong>rejection</strong> only <strong>in</strong> the immediate<br />

vic<strong>in</strong>ity <strong>of</strong> these capillaries (Fig. 5), with subsequent<br />

extension <strong>of</strong> the methylene blue-sta<strong>in</strong>able<br />

epithelial defect from its <strong>in</strong>itial location at one<br />

border all the way across the graft to its opposite<br />

side. When all the sutures are left <strong>in</strong> the centrally<br />

placed lamellar graft, vascular <strong>in</strong>growth occurs<br />

from the entire circumference <strong>of</strong> the limbus to-<br />

Fig. 5. Focal vascularization to the marg<strong>in</strong> <strong>of</strong> a penetrat<strong>in</strong>g allograft has stimulated epithelial<br />

<strong>rejection</strong>. <strong>The</strong> methylene blue-sta<strong>in</strong><strong>in</strong>g epithelial defect (retouched to improve its photographic<br />

reproduction) is restricted to the immediate vic<strong>in</strong>ity <strong>of</strong> the localized vascular <strong>in</strong>growth<br />

<strong>and</strong> extends only to the donor-recipient border on either side. Dur<strong>in</strong>g the ensu<strong>in</strong>g days, its<br />

migration across the entire surface <strong>of</strong> the donor graft could be followed.

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