Enzymatic, Clinical and Histologic Evaluation of Corneal Tissues in Experimental Fungal Keratitis in Rabbits

Gopinathan, Usha; Ramakrishna, T.; Willcox, Mark; Rao, Ch. Mohan; Balasubramanian, D.; Kulkarni, Ajay V.; Vemuganti, Geeta K.; Rao, Gullapalli N

doi:10.1006/exer.2000.0971

Cited by 65 publications

(41 citation statements)

References 27 publications

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“…Matrix metalloproteinases are thought to play a pathological role in the degradation of extracellular matrix components such as basement membrane collagen; same as those found in corneal basement membrane and stroma [18]. They have also been shown to be upregulated in ulcerative fungal keratitis in rabbit as well as in the tear film of horses with ulcerative keratitis and hence are thought to play a probable role in the pathogenesis of fungal keratitis [52,134]. However, the exact role of fungal proteases in mycotic keratitis needs further investigations.…”

Section: Toxigenicitymentioning

confidence: 92%

“…When attempted to compare the presence of fungal proteases in vitro and in vivo, the corneal isolates of A. flavus and F. solani predominantly secreted serine proteases and little metalloproteases in vitro. In vivo, however the protease profile shifted to metalloproteases and no serine protease activity was detected [52]. Matrix metalloproteinases are thought to play a pathological role in the degradation of extracellular matrix components such as basement membrane collagen; same as those found in corneal basement membrane and stroma [18].…”

Section: Toxigenicitymentioning

confidence: 98%

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Pathogenesis of microbial keratitis

Lakhundi

Siddiqui

Khan

2017

Microbial Pathogenesis

171

121

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Microbial keratitis is a sight-threatening ocular infection caused by bacteria, fungi, and protist pathogens. Epithelial defects and injuries are key predisposing factors making the eye susceptible to corneal pathogens. Among bacterial pathogens, the most common agents responsible for keratitis include Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumonia and Serratia species. Fungal agents of corneal infections include both filamentous as well as yeast, including Fusarium, Aspergillus, Phaeohyphomycetes, Curvularia, Paecilomyces, Scedosporium and Candida species, while in protists, Acanthamoeba spp. are responsible for causing ocular disease. Clinical features include redness, pain, tearing, blur vision and inflammation but symptoms vary depending on the causative agent. The underlying molecular mechanisms associated with microbial pathogenesis include virulence factors as well as the host factors that aid in the progression of keratitis, resulting in damage to the ocular tissue. The treatment therefore should focus not only on the elimination of the culprit but also on the neutralization of virulence factors to minimize the damage, in addition to repairing the damaged tissue. A complete understanding of the pathogenesis of microbial keratitis will lead to the rational development of therapeutic interventions. This is a timely review of our current understanding of the advances made in this field in a comprehensible manner. Coupled with the recently available genome sequence information and high throughput genomics technology, and the availability of innovative approaches, this will stimulate interest in this field.

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Section: Toxigenicitymentioning

confidence: 92%

Section: Toxigenicitymentioning

confidence: 98%

Pathogenesis of microbial keratitis

Lakhundi

Siddiqui

Khan

2017

Microbial Pathogenesis

171

121

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“…Clearly, isolates of F. solani and A. flavus from patients with keratitis possess the ability to secrete proteinases (71,119,438). What is not clear, however, is whether these fungi actually secrete these proteinases when infecting corneal tissue and whether such proteinases appreciably influence the outcome of such infections.…”

Section: Putative Agent Factors In the Pathogenesis Of Mycotic Keratitismentioning

confidence: 99%

Current Perspectives on Ophthalmic Mycoses

2003

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Fungi may infect the cornea, orbit and other ocular structures. Species of Fusarium, Aspergillus, Candida, dematiaceous fungi, and Scedosporium predominate. Diagnosis is aided by recognition of typical clinical features and by direct microscopic detection of fungi in scrapes, biopsy specimens, and other samples. Culture confirms the diagnosis. Histopathological, immunohistochemical, or DNA-based tests may also be needed. Pathogenesis involves agent (invasiveness, toxigenicity) and host factors. Specific antifungal therapy is instituted as soon as the diagnosis is made. Amphotericin B by various routes is the mainstay of treatment for life-threatening and severe ophthalmic mycoses. Topical natamycin is usually the first choice for filamentous fungal keratitis, and topical amphotericin B is the first choice for yeast keratitis. Increasingly, the triazoles itraconazole and fluconazole are being evaluated as therapeutic options in ophthalmic mycoses. Medical therapy alone does not usually suffice for invasive fungal orbital infections, scleritis, and keratitis due to Fusarium spp., Lasiodiplodia theobromae, and Pythium insidiosum. Surgical debridement is essential in orbital infections, while various surgical procedures may be required for other infections not responding to medical therapy. Corticosteroids are contraindicated in most ophthalmic mycoses; therefore, other methods are being sought to control inflammatory tissue damage. Fungal infections following ophthalmic surgical procedures, in patients with AIDS, and due to use of various ocular biomaterials are unique subsets of ophthalmic mycoses. Future research needs to focus on the development of rapid, species-specific diagnostic aids, broad-spectrum fungicidal compounds that are active by various routes, and therapeutic modalities which curtail the harmful effects of fungus- and host tissue-derived factors

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“…60 Progression of mycotic keratitis may be augmented by the activation of resident corneal cells or inflammatory cells, particularly polymorphonuclear leucocytes, which release proteinases of different molecular weights, resulting in extensive degradation of the corneal tissue matrix. 61 Current treatment regimens for mycotic keratitis need to be modified to incorporate therapeutic modalities to counter these corneadestroying factors.…”

Section: Eyementioning

confidence: 99%