Photochemical tissue bonding: A potential strategy for treating limbal stem cell deficiency

Li, Zhuoshi; Tien, Ni; Verter, Erol; Redmond, Robert W.; Kochevar, Irene E.; Yao, Min

doi:10.1002/lsm.21066

Cited by 23 publications

(15 citation statements)

References 19 publications

(24 reference statements)

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“…RB (4,5,6,7-tetrachloro-2=,4=,5=,7=-tetraiodofluorescein) is a deeply colored pink compound with a variety of medical uses. It is used as a stain to identify corneal damage (10), in the diagnosis of brucellosis (11), and as a PS to mediate photochemical tissue bonding (12). It has also been used as an anticancer compound (in the dark) given as an intralesional injection into transit melanoma metastases, where it has been shown to activate an antitumor immune response (13).…”

mentioning

confidence: 99%

Potassium Iodide Potentiates Antimicrobial Photodynamic Inactivation Mediated by Rose Bengal in In Vitro and In Vivo Studies

Wen

Zhang

Szewczyk

et al. 2017

Antimicrob Agents Chemother

103

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Rose bengal (RB) is a halogenated xanthene dye that has been used to mediate antimicrobial photodynamic inactivation for several years. While RB is highly active against Gram-positive bacteria, it is largely inactive in killing Gram-negative bacteria. We have discovered that addition of the nontoxic salt potassium iodide (100 mM) potentiates green light (540-nm)-mediated killing by up to 6 extra logs with the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium methicillin-resistant Staphylococcus aureus, and the fungal yeast Candida albicans. The mechanism is proposed to be singlet oxygen addition to iodide anion to form peroxyiodide, which decomposes into radicals and, finally, forms hydrogen peroxide and molecular iodine. The effects of these different bactericidal species can be teased apart by comparing the levels of killing achieved in three different scenarios: (i) cells, RB, and KI are mixed together and then illuminated with green light; (ii) cells and RB are centrifuged, and then KI is added and the mixture is illuminated with green light; and (iii) RB and KI are illuminated with green light, and then cells are added after illumination with the light. We also showed that KI could potentiate RB photodynamic therapy in a mouse model of skin abrasions infected with bioluminescent P. aeruginosa.

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confidence: 99%

Potassium Iodide Potentiates Antimicrobial Photodynamic Inactivation Mediated by Rose Bengal in In Vitro and In Vivo Studies

Wen

Zhang

Szewczyk

et al. 2017

Antimicrob Agents Chemother

103

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“…We have previously demonstrated that this technology can be used to seal wounds in cornea, to bond amniotic membrane to the corneal surface, and for applications in many other tissues. [16][17][18][19][20][21] In this study, we investigated whether photochemical cross-linking of cornea stromal collagen using RB and green light, a process called RGX, increases corneal stiffness. We investigated the processes involved and factors important for clinical application.…”

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confidence: 99%

Collagen Cross-Linking Using Rose Bengal and Green Light to Increase Corneal Stiffness

Cherfan

Verter

Melki³

et al. 2013

Invest. Ophthalmol. Vis. Sci.

Self Cite

147

164

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PURPOSE. Photochemical cross-linking of corneal collagen is an evolving treatment for keratoconus and other ectatic disorders. We evaluated collagen cross-linking by rose bengal plus green light (RGX) in rabbit eyes and investigated factors important for clinical application.METHODS. Rose bengal (RB, 0.1%) was applied to deepithelialized corneas of enucleated rabbit eyes for 2 minutes. The diffusion distance of RB into the stroma was measured by fluorescence microscopy on frozen sections. RB-stained corneas were exposed to green (532-nm) light for 3.3 to 9.9 minutes (50-150 J/cm 2 ). Changes in the absorption spectrum during the irradiation were recorded. Corneal stiffness was measured by uniaxial tensiometry. The spatial distribution of the stromal elastic modulus was assessed by Brillouin microscopy. Viable keratocytes were counted on H&E-stained sections 24 hours posttreatment. RESULTS.RB penetrated approximately 100 lm into the corneal stroma and absorbed >90% of the incident green light. RGX (150 J/cm 2 ) increased stromal stiffness by 3.8-fold. The elastic modulus increased in the anterior approximately 120 lm of stroma. RB was partially photobleached during the 2-minute irradiation, but reapplication of RB blocked light transmission by >70%. Spectral measurements suggested that RGX initiated cross-linking by an oxygen-dependent mechanism. RGX did not decrease keratocyte viability.CONCLUSIONS. RGX significantly increases cornea stiffness in a rapid treatment (@12 minutes total time), does not cause toxicity to keratocytes and may be used to stiffen corneas thinner than 400 lm. Thus, RGX may provide an attractive approach to inhibit progression of keratoconus and other ectatic disorders.

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“…This pink xanthene dye is used for the diagnosis of damage in corneal ( Doughty, 2013 ), brucellosis ( Ducrotoy and Bardosh, 2017 ). Rose Bengal in combination with the green light has been extensively studied with respect to photochemical tissue bonding and corneal transplants ( Gu et al, 2011 ; Gallego-Munoz et al, 2017 ). This compound was also studied in anti-tumor immune responses in melanoma models ( Liu et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…RB possess a strong absorption band at 550 nm, and strong molar absorption coefficient (95,000 dm 3 mol −1 cm −1 ) ( Ludvikova et al, 2016 ). RB properties have been extensively investigated in technology known as photochemical tissue bonding in tissue repair ( Gu et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Rose Bengal-Mediated Photoinactivation of Multidrug Resistant Pseudomonas aeruginosa Is Enhanced in the Presence of Antimicrobial Peptides

et al. 2018

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Due to the overuse of antibiotics in medicine and food production, and their targeted mechanism of action, an increasing rate in spreading of antibiotic resistance genes has been noticed. This results in inefficient therapy outcomes and higher mortality all over the world. Pseudomonas aeruginosa (carbapenem-resistant) is considered one of the top three critical species according to the World Health Organization’s priority pathogens list. This means that new drugs and/or treatments are needed to tackle infections caused by this bacterium. In this context search for new/alternative approaches that would overcome resistance to classical antimicrobials is of prime importance. The use of antimicrobial photodynamic inactivation (aPDI) and antimicrobial peptides (AMPs) is an efficient strategy to treat localized infections caused by multidrug-resistant P. aeruginosa. In this study, we have treated P. aeruginosa cells photodynamically in the presence and in the absence of AMP (CAMEL or pexiganan). The conditions for aPDI were as follows: rose bengal (RB) as a photosensitizing agent at 1–10 μM concentration, and subsequent irradiation with 514 nm-LED at 23 mW/cm2 irradiance. The analysis of cell number after the treatment has shown that the combined action of RB-mediated aPDI and cationic AMPs reduced the number of viable cells below the limit of detection (<1log10 CFU/ml). This was in contrast to no reduction or partial reduction after aPDI or AMP applied separately. Students t-test was applied to test the statistical significance of the results. Noteworthy, our treatment proved to be effective against all 35 clinical isolates of P. aeruginosa tested within this study, including those characterized as multiresistant. Moreover, we demonstrated that such treatment is safe and does not violate the growth dynamics of human keratinocytes (77.3–97.64% survival depending on the concentration of the studied compounds or their mixtures).

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Photochemical tissue bonding: A potential strategy for treating limbal stem cell deficiency

Abstract: Bonding LSC grafts with PTB produced improved outcomes compared to suture attachment. This light-activated method is a promising modality for treating patients with LSCD.

Cited by 23 publications

References 19 publications

Potassium Iodide Potentiates Antimicrobial Photodynamic Inactivation Mediated by Rose Bengal in In Vitro and In Vivo Studies

Potassium Iodide Potentiates Antimicrobial Photodynamic Inactivation Mediated by Rose Bengal in In Vitro and In Vivo Studies

Collagen Cross-Linking Using Rose Bengal and Green Light to Increase Corneal Stiffness

Rose Bengal-Mediated Photoinactivation of Multidrug Resistant Pseudomonas aeruginosa Is Enhanced in the Presence of Antimicrobial Peptides

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