ALTERATION TUMOR NECROSIS FACTOR-ALPHA AND MATRIX METALLOPROTEINASE-9 EXPRESSION IN CANDIDA KERATITIS WITH AND WITHOUT STEROID ADMINISTRATION
Keywords:Candida keratitis, Tumor necrosis factor-alpha expression, Severity
Objective: The objective of the study was to determine the severity level of keratitis, inflammatory response, and clinical feature of fungal keratitis associated with tumor necrosis factor-alpha (TNF-α) and matrix metalloproteinase (MMP)-9 expression, with and without steroid administration.
Methods: The mice corneas were inoculated with 108 CFU Candida albicans (CA), divided into two groups, one group with steroid administration and other group without steroid, and uninoculated cornea is used as the control. The mice eyes were observed for the development of keratitis and assess the clinical score to categorize severity level of the keratitis. After 7 days, they were enucleated for analysis of TNF-α and MMP-9 expression with immunohistochemistry and histopathologic examination.
Results: Results show that the group inoculated with Candida and steroid has more moderate and severe level of keratitis compared to the group inoculated with Candida only. The final clinical score in the group of CA injected with steroid was 5–12 with mean 8.89 (2.67). The histopathological examination confirmed the presence of prominent inflammatory response in steroid group. The mean of TNF-α expression in Candida keratitis with and without steroid injections is 50.1 (8.09) and 31.7 (6.89) consecutively, compared to 16.8 (1.58) of control group. The mean of MMP-9 expression in Candida keratitis with steroid injection is higher than Candida keratitis group without steroid injection and control group, which are 46.6 (4.3), 37.8 (4.96), and 17.2 (1.73), respectively. This difference is statistically significant.
Conclusion: Administration of steroids to Candida keratitis has negative effect to corneal tissue, resulting in more severe inflammatory response associated with increased TNF-α and MMP-9 expressions.
Ansari Z, Miller D, Galor A. Current thoughts in fungal keratitis: Diagnosis and treatment. Curr Fungal Infect Rep 2013;7:209-18.
Achyarya Y, Achyarya B, Karki P. Fungal keratitis: Study of increasing trend and common determinants. Nepal J Epidemiol 2017;7:685-93.
Lalitha P, Prajna NV, Kabra A. Risk factors for treatment outcome in fungal keratitis. Ophthalmology 2006;113:526-30.
Kenia VP, Kenia RV, Pirdankar OH. Diagnosis and management protocol of acute corneal ulcer. Int J Health Sci Res 2020;10:69-78.
Nielsen SE, Nielsen E, Julian HO, Lindegaard J, Hojgaard K, Ivarsen A, et al. Incidence and clinical characteristic of fungal keratitis in a Danish population from 2000-2013. Acta Ophthalmol 2015;93:54-8.
Cho CH, Lee SB. Clinical analysis of microbiologically proven fungal keratitis according to prior topical steroid use: A retrospective study in South Korea. Br Med J 2019;19:207.
Qin Y, Zhang L, Xu Z, Zhang J, Jiang Y, Cao Y, et al. Innate immune cell response upon Candida albicans infection. Virulence 2016;7:512-26.
Stern ME, Schaumburg CS, Dana R, Calonge M, Niederkorn JY, Pflufelder SC. Autoimmunity at the ocular surface: Pathogenesis and regulation. Mucosal Immunol 2010;3:425-42.
Hassell JR, Birk DE. The molecular basis of corneal transparency. Exp Eye Res 2010;91:326-35.
Zhang Y, Liang Q, Liu Y, Pan Z, Baudouin C, Labbe A, et al. Expression of cytokine in aqueous humor from fungal keratitis patients. BMC Ophthalmol 2018;18:105.
Mitchel BM, Wu TG, Chong E, Pate JC, Wilhelmus KR. Expression of matrix metalloproteinase 2 and 9 in experimental corneal injury and fungal keratitis. Cornea 2007;26:589-93.
Dong X, Shi W, Zeng Q, Xie L. Roles of adherence and matrix metalloproteinase in growth patterns of fungal pathogens in cornea. Curr Eye Res 2005;30:613-20.
Srinivas D. Therapeutic keratoplasty in fungal keratitis. J Evid Based Med Healthc 2014;1:1047-60.
Shinivasan M. Corticosteroids: A possible treatment for corneal ulcers? Expert Rev Opthalmol 2012;7:1-3.
Palliora S, Henry CR, Amescua G, Alfonso EC. Role of steroid in the treatment of bacterial keratitis. Clin Ophthalmol 2016;10:179-86.
Srinivasan M, Mascarenhas J, Rajaraman R. Corticosteroid for bacterial keratitis. The steroid for corneal ulcers trial (SCUT). Arch Ophthalmol 2012;130:143-50.
Sarchahi AA, Parizi AM, Eghtedan M. Effect of different treatment regimen with dexamethasone and acetylcysteine on corneal wound healing in rabbits. Iran J Med Sci 2011;36:188-95.
Austin A, Lietman T. Update on the management of infectious keratitis. Ophthalmology 2017;124:1678-89.
Kimura K, Morita Y, Orita T, Haruta J, Takeji Y, Sonoda KH. Protection of human corneal epithelial cells from TNF-α-induced disruption of barrier function by rebamipide. Invest Ophthalmol Vis Sci 2013;54:2752-60.
Yuan X, Mitchell BM, Wilhelmus KR. Expression of matrix metalloproteinases during experimental Candida albicans keratitis. Invest Ophthalmol Vis Sci 2009;50:737-42.
Kaufman HE. The practical detection of MMP-9 diagnoses ocular surface disease and may help prevent its complications. Cornea 2013;32:211-6.
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