Fangli Fan1,2, Xiaodan Huang1, Kelan Yuan1, Binbin Zhu1, Yingying Zhao1, Renjian Hu1, Ting Wan1, Lian Zhu3, Xiuming Jin1. 1. Eye Center, Affiliated Second Hospital, School of Medicine, Zhejiang University, Hangzhou, China. 2. Department of Ophthalmology, First People's Hospital of Yuhang District, Hangzhou, China. 3. Department of Ophthalmology, The people's Hospital of SND, Suzhou, China.
Abstract
Purpose: To evaluate whether glucocorticoids affect the prognosis of fungal keratitis by inhibiting the formation of neutrophil extracellular traps (NETs). Methods: A mouse model of Candida albicans (C.albicans) keratitis was established. Animals were randomly assigned to treatment with 0.1% dexamethasone (DXM) eye drops and normal saline (3 times each day for 3 days). The effects of DXM on fungal keratitis were assessed using clinical scores, immunofluorescence staining, histopathological examination, scanning electron microscopy (SEM), and pathogen burden assay. All the analyses were performed using SPSS software version 17.0 (Chicago, IL). Results: NETs formation was noteworthy in the cornea lesions of fungal keratitis. The clinical score of the DXM-treated group was significantly higher than that of the control group (P < .05). During the measured period, corneas from DXM-treated group contained more C.albicans than those from the control group by histology and pathogen burden assay. Compared with the control group, the DXM treatment group had a higher depth of infiltration of C.albicans. Histological and immunofluorescence staining showed that there were fewer neutrophils in the cornea focus of DXM-treated group (P < .05）, and the number of NETs formed in scrapings from control group was higher than that in the DXM treatment group on day 3 (P < .05, Z = -3.56)) and day 5 (P < .05, Z = -3.69). In a similar amount of cell scraping, the NETs of neutrophils formation from the DXM-treated group were also less than that from the control group. Conclusion: Our results indicated that NETs were involved in the immune response in C.albicans keratitis. Glucocorticoids may exacerbate fungal keratitis not only by increasing fungal aggressivity and reducing the infiltration of neutrophils but also by inhibiting the formation of NETs.
Purpose: To evaluate whether glucocorticoids affect the prognosis of fungal keratitis by inhibiting the formation of neutrophil extracellular traps (NETs). Methods: A mouse model of Candida albicans (C.albicans) keratitis was established. Animals were randomly assigned to treatment with 0.1% dexamethasone (DXM) eye drops and normal saline (3 times each day for 3 days). The effects of DXM on fungal keratitis were assessed using clinical scores, immunofluorescence staining, histopathological examination, scanning electron microscopy (SEM), and pathogen burden assay. All the analyses were performed using SPSS software version 17.0 (Chicago, IL). Results: NETs formation was noteworthy in the cornea lesions of fungal keratitis. The clinical score of the DXM-treated group was significantly higher than that of the control group (P < .05). During the measured period, corneas from DXM-treated group contained more C.albicans than those from the control group by histology and pathogen burden assay. Compared with the control group, the DXM treatment group had a higher depth of infiltration of C.albicans. Histological and immunofluorescence staining showed that there were fewer neutrophils in the cornea focus of DXM-treated group (P < .05）, and the number of NETs formed in scrapings from control group was higher than that in the DXM treatment group on day 3 (P < .05, Z = -3.56)) and day 5 (P < .05, Z = -3.69). In a similar amount of cell scraping, the NETs of neutrophils formation from the DXM-treated group were also less than that from the control group. Conclusion: Our results indicated that NETs were involved in the immune response in C.albicanskeratitis. Glucocorticoids may exacerbate fungal keratitis not only by increasing fungal aggressivity and reducing the infiltration of neutrophils but also by inhibiting the formation of NETs.
Authors: Rebecca Dowey; Joby Cole; A A Roger Thompson; Rebecca C Hull; Chenghao Huang; Jacob Whatmore; Ahmed Iqbal; Kirsty L Bradley; Joanne McKenzie; Allan Lawrie; Alison M Condliffe; Endre Kiss-Toth; Ian Sabroe; Lynne R Prince Journal: ERJ Open Res Date: 2022-04-04