Expression of SPARC and MMP9 in Stevens-Johnson syndrome chronic ocular sequelae undergoing cultivated oral mucosal epithelial transplantation

Abstract

Purpose : Molecular pathogenesis remains unknown in chronic ocular sequelae in Stevens Johnson Syndrome(SJS). Persistent underlying conjunctival inflammation and tear deficiency in SJS affects the prognosis of visual rehabilitation surgeries. Secreted protein acidic and rich in cysteine(SPARC), an extracellular matrix(ECM) protein is a key modulator of fibrosis and tissue scarring. Matrix metalloproteinase 9(MMP9) gets activated in SPARC mediated wound healing and tumor metastasis. The current study evaluates their role in chronic SJS cases.

Methods : Pannus tissues were excised from 45 SJS eyes undergoing COMET and clinico-pathological parameters were examined. Immunohistochemistry(IHC) and Real Time PCR were performed for SPARC and MMP9 expression. Cadaveric cornea was used as a control. Postoperative MMP9 levels were assessed in tears using Inflammadry MMP9 assay. Statistical correlation was done with clinicopathological parameters and follow up.

Results : Mean age of patients was 25 ± 11.7 years. The primary causative agent in inciting SJS was NSAIDS(55%).The logMAR BCVA improved post COMET in 82.2% eyes and 55.5% eyes were removed from blindness category. Total severity score improved in 88.8% eyes. Cytoplasmic MMP9 and SPARC overexpression was seen in pannus epithelium of 48.9% and 44.4% eyes while in stroma, 57.7% and 77.7% eyes. Epithelial MMP9 expression correlated with preoperative corneal vascularization and keratinization while stromal expression correlated with hyperaemia and symblepharon (p< 0.05). SPARC epithelial expression correlated with conjunctivalization while stromal expression correlated with fibrosis (p<0.05). MMP9 and SPARC RNA expression correlated with fibrosis and epithelial hyperplasia(p<0.05). On Univariate analysis, MMP9 and SPARC epithelial immunoexpression and MMP9 RNA over expression correlated with poor COMET graft survival(p<0.05). MMP9 Inflammadry assay in SJS post COMET eyes showed 83.3% positivity.

Conclusions : Ours is the first study to reveal the possible role of SPARC and MMP9 in promoting tissue scarring and remodelling in SJS chronic eyes. Their over-expression correlated with poor visual acuity outcomes of COMET. MMP9 overexpression in tear indicates persistent secretion of MMP9 in SJS post COMET eyes leading to prolonged dryness. Our results may help in developing targeted therapeutics for chronic SJS.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.