BACKGROUND Fungal keratitis is basically treated by medications. Several cases of fungal keratitis were reported around the world to have been treated successfully by corneal graft--penetrating keratoplasty (PKP). Studies have shown that PKP is a useful treatment, preserves eye globe integrity, and rehabilitates vision in patients with advanced fungal keratitis. AIM To study the use of penetrating keratoplasty for the treatment of severe fungal keratitis that could not be cured by antifungal medication. METHODS The authors conducted a retrospective analysis of all cases (five cases) of severe fungal keratitis treated and followed-up at the Department of Ophthalmology, Soroka University Medical Center during 2007 and 2008, in which therapeutic PKP was performed. There were one male and 4 females. The age range was between 27 and 78 years. The follow-up period ranged from 4 to 15 months. RESULTS Corneal graft remained clear during follow-up in most patients. There was no recurrence of fungal infection and the visual acuity ranged from counting fingers (FC) from 50 cm to 6/36. Complications in some patients included graft rejection in one patient with re-graft which remained clear during follow-up period of 6 months, another patient had a minimal partial graft rejection and incipient cataract which didn't necessitate further intervention. DISCUSSION AND CONCLUSIONS PKP is an effective treatment for fungal keratitis that does not respond to antifungal medication. Early surgical intervention before deterioration is recommended.

Treatment of fungal keratitis by penetrating keratoplasty

Fungal keratitis: Pathogenesis, diagnosis and prevention.

Structural aspects and biomedical applications of microfungal lectins

Purification and characterization of a mitogenic lectin from Penicillium duclauxii

Infections due to microfungi are of serious concern in many parts of the world. Many species of microfungi are known to cause systemic infection in human beings. Pathogenic microorganisms employ various molecular strategies for colonizing a susceptible host. Recent studies have shown the importance of lectins from microfungi that enable the pathogen to interact with the host, resulting in host immune response. These fungal lectins or adhesins show specific affinities to the glycans present on the membrane proteins or lipids. Binding of the pathogen to the receptors, probably toll-like receptors or dectins, present on the host cell surface triggers/initiates a cascade of signalling pathways, leading to the activation of transcription factors such as NF-κB resulting in the release of proinflammatory cytokines which in turn recruit cells of the immune system to the site of microbial insult to combat the pathogen or resulting in pathogenesis. In this review, we will focus on the interaction between fungal lectins and the host glycans initiating pathogenesis and how the host immune system tries to suppress the pathogenesis.

An overview of lectin-glycan interactions: a key event in initiating fungal infection and pathogenesis.

A core-fucose-specific lectin, CSL from Cephalosporium curvulum, has been reported earlier. Here we assign the role for CSL and another lectin AOL, from pathogenic fungus Aspergillus oryzae, in causing mycotic keratitis. CSL and AOL show strong binding to immortalized and primary human corneal epithelial cells (HCECs) which are inhibited by asialofetuin, confirming their glycan-mediated binding. CSL and AOL showed increase in viability at lower concentrations (0.07 µg/ml) whereas at higher concentrations (0.15 µg/ml and 0.30 µg/ml), have inhibitory effect on immortalized HCECs. Lectin-mediated effect was comparable with the effect induced by the Colony Forming Units (CFUs) of C. curvulum and A. oryzae. CFUs induced more than 1.5-fold increase in HCECs proliferation. Both lectins and fungal CFUs induce secretion of proinflammatory cytokines IL6 and IL8 implicated in ocular diseases. This was supported by upregulation of TLR2 and 4 by lectins as revealed by flow cytometry and RT-PCR. CSL and AOL mediate host-pathogen interactions leading to mycotic keratitis. The mechanism of pathogenesis is possibly initiated through surface binding of mycelia through the lectins to TLR2/4 followed by upregulation of proinflammatory cytokines IL6, IL8 and TLR2 and 4. Understanding the mechanism of pathogenesis is of clinical significance in designing and developing therapeutic strategy to control the infection.

Mitogenic lectins from Cephalosporium curvulum (CSL) and Aspergillus oryzae (AOL) mediate host–pathogen interactions leading to mycotic keratitis

Sclerotium rolfsii lectin (SRL) is a lectin isolated from the fungus Sclerotium rolfsii and has exquisite binding specificity towards the oncofetal Thomsen-Friedenreich antigen (TF-Ag; Galβ1-3GalNAcα-O-Ser/Thr) and its derivatives. Previous studies have shown that SRL inhibits the proliferation of human colon, breast and ovarian cancer cells in vitro and suppresses tumour growth in mice when introduced intratumourally. The present study assessed the effect of SRL on tumour growth when introduced intraperitoneally in BALB/c nude mice and investigated the pharmacokinetics and biodistribution of SRL in Swiss albino mice. When 9 doses of SRL (30 mg/kg body weight/mice) was administered to BALB/c nude mice bearing human colon cancer HT-29 xenografts, a substantial reduction in tumour size was observed. A 35.8% reduction in tumour size was noted in the treated animals after 17 days. SRL treatment also inhibited angiogenesis, and the tumours from the treated animals were observed to carry fewer blood vessels and express less angiogenesis marker protein CD31, than that from the control animals. Pharmacokinetics and biodistribution analysis revealed that SRL was detected in the serum after 1 h and its level peaked after 24 h. SRL was not detected in any of the organs apart from the kidney where a trace amount was detected after 24 h of SRL injection. No significant changes were observed in any of the biochemical parameters tested including SGOT, SGPT, LDH, CREAT and BUN in the SRL-treated mice compared to these levels in the controls. This suggests that SRL has good potential to be developed as a therapeutic agent for cancer treatment and warrant further investigations in vivo and subsequent clinical trials.

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Preeti Laha

Papers

Mitogenic lectins from Cephalosporium curvulum (CSL) and Aspergillus oryzae (AOL) mediate host–pathogen interactions leading to mycotic keratitis

Pharmacokinetics, biodistribution and antitumour effects of Sclerotium rolfsii lectin in mice