Fungal corneal ulcer is one of the leading causes of corneal blindness in developing countries.Corneal scars such as leukoplakia are formed due to inflammation,oxidative stress and non-directed repair,which seriously ...Fungal corneal ulcer is one of the leading causes of corneal blindness in developing countries.Corneal scars such as leukoplakia are formed due to inflammation,oxidative stress and non-directed repair,which seriously affect the patients'subsequent visual and life quality.In this study,drawing inspiration from the oriented structure of collagen fibers within the corneal stroma,we first proposed the directional arrangement of CuTA-CMHT hydrogel system at micro and macro scales based on the 3D printing extrusion method combined with secondary patterning.It played an antifungal role and induced oriented repair in therapy of fungal corneal ulcer.The results showed that it effectively inhibited Candida albicans,Aspergillus Niger,Fusarium sapropelum,which mainly affects TNF,NF-kappa B,and HIF-1 signaling pathways,achieving effective antifungal functions.More importantly,the fibroblasts interacted with extracellular matrix(ECM)of corneal stroma through formation of focal adhesions,promoted the proliferation and directional migration of cells in vitro,induced the directional alignment of collagen fibers and corneal stromal orthogonally oriented repair in vivo.This process is mainly associated with MYLK,MYL9,and ITGA3 molecules.Furthermore,the downregulation the growth factors TGF-βand PDGF-βinhibits myofibroblast development and reduces scar-type ECM production,thereby reducing corneal leukoplakia.It also activates the PI3K-AKT signaling pathway,promoting corneal healing.In conclusion,the oriented CuTA-CMHT hydrogel system mimics the orthogonal arrangement of collagen fibers,inhibits inflammation,eliminates reactive oxygen species,and reduces corneal leukoplakia,which is of great significance in the treatment of fungal corneal ulcer and is expected to write a new chapter in corneal tissue engineering.展开更多
AIM： To evaluate the efficacy of modified corneal ulcer debridement in superficial fungal keratitis unresponsive to medications.METHODS： A total of 209 patients（209 eyes） with fungal keratitis, involving no more t...AIM： To evaluate the efficacy of modified corneal ulcer debridement in superficial fungal keratitis unresponsive to medications.METHODS： A total of 209 patients（209 eyes） with fungal keratitis, involving no more than 50% of the stromal depth and not responding to antifungal agents for 2 wk, were recruited in this retrospective, noncomparative study. The patients were treated with modified corneal ulcer debridement. All visible corneal infiltrates were removed under an operating microscope to obtain a clean stromal bed and smooth incised edges. Antifungal drugs were used immediately after surgery. Healing time of the ulcers was recorded. Fungal recurrence, visual acuity, corneal thickness and risk factors for treatment failure were monitored.RESULTS： The follow-up was 13.6±5.8m o. The corneal ulcers healed in 195 of 209 eyes（93.3%）, with a mean healing time of 8.4±6.8 d. The other 14 eyes were further treated by penetrating keratoplasty（PK）（1 eye）, anterior lamellar keratoplasty（LK）（7 eyes）, conjunctival flap covering（4 eyes） or amniotic membrane transplantation（2 eyes）. The best corrected visual acuity（BCVA） was ≥20/70 in 80.3% of the eyes, ≥20/40 in 56.9% of the eyes, and ≥20/25 in 27.3% of the eyes. The corneas at the lesions became thinner, but all in the safe range. No fungal recurrence or corneal ectasis developed during the follow-up. The risk of treatment failure was higher in patients with preoperative hypopyon（P=0.036） and ever using steroid（P=0.025）.CONCLUSION： Modified surgical debridement is a simple and effective method for the treatment of superficial fungal infection of the cornea, with improved visual acuity and no recurrence. Such an intervention in time can rapidly control fungal infection and largely shorten corneal ulcer healing time.展开更多
基金Tsinghua Berkeley Shenzhen Institute and the Project of Basic Research of Shenzhen,China(JCYJ20170412101508433&JCYJ20180507183655307)National Key Research and Development Program of China(2023YFE0203100)National Natural Science Foundation of China(Grant Nos.82271051,82070926).
文摘Fungal corneal ulcer is one of the leading causes of corneal blindness in developing countries.Corneal scars such as leukoplakia are formed due to inflammation,oxidative stress and non-directed repair,which seriously affect the patients'subsequent visual and life quality.In this study,drawing inspiration from the oriented structure of collagen fibers within the corneal stroma,we first proposed the directional arrangement of CuTA-CMHT hydrogel system at micro and macro scales based on the 3D printing extrusion method combined with secondary patterning.It played an antifungal role and induced oriented repair in therapy of fungal corneal ulcer.The results showed that it effectively inhibited Candida albicans,Aspergillus Niger,Fusarium sapropelum,which mainly affects TNF,NF-kappa B,and HIF-1 signaling pathways,achieving effective antifungal functions.More importantly,the fibroblasts interacted with extracellular matrix(ECM)of corneal stroma through formation of focal adhesions,promoted the proliferation and directional migration of cells in vitro,induced the directional alignment of collagen fibers and corneal stromal orthogonally oriented repair in vivo.This process is mainly associated with MYLK,MYL9,and ITGA3 molecules.Furthermore,the downregulation the growth factors TGF-βand PDGF-βinhibits myofibroblast development and reduces scar-type ECM production,thereby reducing corneal leukoplakia.It also activates the PI3K-AKT signaling pathway,promoting corneal healing.In conclusion,the oriented CuTA-CMHT hydrogel system mimics the orthogonal arrangement of collagen fibers,inhibits inflammation,eliminates reactive oxygen species,and reduces corneal leukoplakia,which is of great significance in the treatment of fungal corneal ulcer and is expected to write a new chapter in corneal tissue engineering.
基金Supported by the Natural Science Foundation of Shandong Province(No.ZR2014HQ059)
文摘AIM： To evaluate the efficacy of modified corneal ulcer debridement in superficial fungal keratitis unresponsive to medications.METHODS： A total of 209 patients（209 eyes） with fungal keratitis, involving no more than 50% of the stromal depth and not responding to antifungal agents for 2 wk, were recruited in this retrospective, noncomparative study. The patients were treated with modified corneal ulcer debridement. All visible corneal infiltrates were removed under an operating microscope to obtain a clean stromal bed and smooth incised edges. Antifungal drugs were used immediately after surgery. Healing time of the ulcers was recorded. Fungal recurrence, visual acuity, corneal thickness and risk factors for treatment failure were monitored.RESULTS： The follow-up was 13.6±5.8m o. The corneal ulcers healed in 195 of 209 eyes（93.3%）, with a mean healing time of 8.4±6.8 d. The other 14 eyes were further treated by penetrating keratoplasty（PK）（1 eye）, anterior lamellar keratoplasty（LK）（7 eyes）, conjunctival flap covering（4 eyes） or amniotic membrane transplantation（2 eyes）. The best corrected visual acuity（BCVA） was ≥20/70 in 80.3% of the eyes, ≥20/40 in 56.9% of the eyes, and ≥20/25 in 27.3% of the eyes. The corneas at the lesions became thinner, but all in the safe range. No fungal recurrence or corneal ectasis developed during the follow-up. The risk of treatment failure was higher in patients with preoperative hypopyon（P=0.036） and ever using steroid（P=0.025）.CONCLUSION： Modified surgical debridement is a simple and effective method for the treatment of superficial fungal infection of the cornea, with improved visual acuity and no recurrence. Such an intervention in time can rapidly control fungal infection and largely shorten corneal ulcer healing time.
