Abnormal keratocytes and stromal inflammation in chronic phase of severe ocular surface diseases with stem cell deficiency

Abstract

Background/Aims: Stevens-Johnson syndrome (SJS), ocular cicatricial pemphigoid (OCP) and alkali burns are associated with chronic, severe inflammation of the ocular surface that occasionally lead to corneal stem cell deficiencies. The corneal stroma in these diseases has not been studied comprehensively. The purpose of this study was to determine whether the keratocytes in the stroma were normal and whether the stroma remained inflamed in the chronic phase of these diseases. Methods: Five pathological corneas, two with SJS, two with OCP and one with an alkali burn were examined. Corneal specimens were obtained during lamellar keratoplasty and the histological sections were immunostained with antibodies against CD34 and several cell surface antigens. The level of expression of proteoglycans (lumican, keratocan, biglycan) and chemokines (monocyte chemoattractant protein 1, macrophage inflammatory protein (MIP) 1a, MIP1b) were examined by quantitative real-time RT-PCR. Results: The number of CD34-positive cells in the stroma was decreased and the expression level of biglycan increased in all of the pathological corneas. The numbers of CD45-positive and CD14-positive cells were increased in four of the five pathological corneas. The expression level of MIP1a and MIP1b were markedly increased in all of the pathological corneas. Conclusions: These findings indicate that the keratocytes are abnormal and inflammation is still present in the corneal stroma in the chronic phase of SJS, OCP and alkali burns.Stevens-Johnson syndrome (SJS) and ocular cicatricial pemphigoid (OCP) of the cornea occasionally result in total limbal stem cell deficiency that often leads to severe ocular complications, which do not respond to classic treatment either in the acute phase or in the chronic phase.1-4 The outcome of surgery for these diseases is also poor, 5 suggesting that the prolonged inflammation and severe dry eye or abnormal epithelial differentiation is not conducive to good surgical results. 6 Severe alkali burns of the cornea also result in limbal stem cell deficiency and poor prognosis in some cases.7-10 Compared with immunologically driven diseases such as SJS, however, the operative outcome is reported to be better especially when an autograft limbal transplantation is performed. 11-13In the chronic phase of SJS and chemical injury, inflammatory cells infiltrate into the conjunctivalised corneal epithelium.14 The outer layer of the corneal stroma under a pannus is occasionally invaded by blood vessels and opacities develop in these areas, but the pathological alterations in these areas have not been studied in detail. We hypothesised that abnormalities of keratocytes and persistent inflammation exist in the corneal stroma during the chronic phase of ocular surface diseases. To determine the pathological state of corneal stroma of eyes with severe ocular surface diseases covered by a pannus in the chronic phase, we examined five pathological corneas. If our hypothesis is correct, it should be possible to alter the e...

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