Inflammation and oxidative stress in corneal tissue in experimental keratitis due to Fusarium solani: Amelioration following topical therapy with voriconazole and epigallocatechin gallate

Abstract

Combined antifungal and antioxidant therapy may help to reduce oxidative stress in fungal keratitis. Experimental Fusarium solani keratitis was induced by application of F. solani conidia to scarified cornea (right eye) of 16 rabbits (another four rabbits were negative controls [Group I]). Five days later, F. solani-infected animals began receiving hourly topical saline alone (Group II), voriconazole (10 mg/mL) alone (Group III), epigallocatechin gallate (EGCG, 10 mg/mL) alone (Group IV) or voriconazole and EGCG (Group V). Twenty days post-inoculation, corneal lesions were graded. After animal sacrifice, excised corneas underwent histopathological and microbiological investigations. Corneal tissue levels/activities of interleukin 1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α) gene mRNA transcripts, matrix metalloproteinase (MMP) 2 and 9 proteins, malondialdehyde (MDA) and reduced glutathione (GSH), and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), were also measured. Clinical and histopathological scores (severity of corneal lesions; [P < .05]) and mean levels (P < .05) of IL-1β and TNF-α mRNA transcripts, MMP 2, MMP 9 and MDA were Group II > Groups IV and III > Groups V and I. Mean SOD, CAT, GPx and GSH levels (P < .05) were Group II < Groups IV and III < Groups V and I. Topical voriconazole with EGCG apparently reduces inflammation in experimental F. solani keratitis, as manifested by improved clinical, histological, microbiological and molecular parameters.

VEGF-B is a potent antioxidant

“…Indeed, studies have shown that oxidative stress in the degenerating retinas is considerably higher than that of normal retinas. Apart from retinal degeneration, oxidative damage is also a key pathology of many other diseases, such as age-related macular degeneration, glaucoma, diabetic retinopathy (31), retinopathy of prematurity (30), dry eye syndrome (32), keratitis (33), and retinopathy after radiotherapy (34). Different antioxidants have been used in the clinic to treat patients with degenerative diseases (35).…”

Rabbit Fungal Keratitis Model of Fusarium solani Tested Against Three Commercially Available Antifungal Drugs

“…The reports have been published in the literature showing the effectiveness of voriconazole in the animal model, 15 , 16 , 18 , 21 , 22 and most of the animal models used 3 days of a waiting period to initiate the treatment which is indicated for treating superficial infections. 15 , 16 , 21 A report suggested that filamentous fungi tended to grow toward the anterior chamber as the infection progresses.…”

“… 13 – 18 A few studies have used subconjunctival injection of steroids to suppress the local immunity before infection into the corneal stroma 19 – 21 while others used systemic immunosuppression of dexamethasone or cortisone to suppress the systemic immunity. 22 , 23 Hence, we have used an integrated approach to achieve a successful F. solani rabbit keratitis model and reported a useful, reproducible rabbit model of F. solani keratitis which we used to compare three commonly used commercially available antifungals.…”

Alternative Therapeutic Interventions: Antimicrobial Peptides and Small Molecules to Treat Microbial Keratitis

“…Treatment of infected mice cornea with baicalein significantly reduced fungal growth, biofilm formation, adhesion, and suppressing inflammatory responses via downregulating the thymic stromal lymphopoietin (TSLP)/TSLP receptor (TSLPR) pathway (Zhu et al, 2021). Epigallocatechin gallate (EGCG) is a polyphenol obtained from the green tea is known to have good antioxidant and anti-inflammatory activity (Ruban et al, 2018). Topical administration of voriconazole along with EGCG showed the inhibition of F. solani-induced keratitis by reducing the fungal growth and inflammatory responses.…”