Keratoconus and Other Corneal Diseases: Pharmacologic Cross-Linking and Future Therapy

Hsu, Kimberly; Sugar, Joel

doi:10.1007/164_2016_23

Cited by 5 publications

(5 citation statements)

References 144 publications

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“…Another common method for polymer crosslinking, specifically collagen, involves using riboflavin as a photoreactive group. Riboflavin (vitamin B2) is mainly used in ophthalmic and tissue engineering applications to enhance corneal strength and tailor mechanical properties of collagen constructs (Tirella et al, 2012;Rich et al, 2014;Hsu and Sugar, 2017). Recently, it has also been used for crosslinking GFs, such as EGF, bFGF, and TGF-β1, onto collagen-based biomaterials (Bertolo et al, 2015;Fernandes-Cunha et al, 2017).…”

Section: Light-induced Immobilizationmentioning

confidence: 99%

“…During exposure to UV light, oxygen species are released from the carboxylic groups of riboflavin, leading to the generation of light-activated riboflavin and single reactive oxygens. These highly reactive molecules then induce the formation of covalent bonds by reacting with the amino acids from the GF and collagen (Rich et al, 2014;Hsu and Sugar, 2017). It has been suggested that possible vulnerable amino acids to photochemical crosslinking using riboflavin include tyrosine, histidine, cysteine and methionine (Rich et al, 2014).…”

Section: Light-induced Immobilizationmentioning

confidence: 99%

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Immobilization of Growth Factors for Cell Therapy Manufacturing

Enriquez-Ochoa

Robles-Ovalle

Mayolo‐Deloisa

et al. 2020

Front. Bioeng. Biotechnol.

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Cell therapy products exhibit great therapeutic potential but come with a deterring price tag partly caused by their costly manufacturing processes. The development of strategies that lead to cost-effective cell production is key to expand the reach of cell therapies. Growth factors are critical culture media components required for the maintenance and differentiation of cells in culture and are widely employed in cell therapy manufacturing. However, they are expensive, and their common use in soluble form is often associated with decreased stability and bioactivity. Immobilization has emerged as a possible strategy to optimize growth factor use in cell culture. To date, several immobilization techniques have been reported for attaching growth factors onto a variety of biomaterials, but these have been focused on tissue engineering. This review briefly summarizes the current landscape of cell therapy manufacturing, before describing the types of chemistry that can be used to immobilize growth factors for cell culture. Emphasis is placed to identify strategies that could reduce growth factor usage and enhance bioactivity. Finally, we describe a case study for stem cell factor.

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Section: Light-induced Immobilizationmentioning

confidence: 99%

Section: Light-induced Immobilizationmentioning

confidence: 99%

Immobilization of Growth Factors for Cell Therapy Manufacturing

Enriquez-Ochoa

Robles-Ovalle

Mayolo‐Deloisa

et al. 2020

Front. Bioeng. Biotechnol.

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“…Corneal cross-linking has already shown promising efficacy on various ectatic diseases, by halting progression and stabilizing the cornea [ 15 ]. This technique also has benefits in infectious keratitis, including keratitis caused by bacteria, fungi, and Acanthamoeba , by blocking corneal melting together with antimicrobial properties [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of voriconazole and corneal cross-linking on Phialophora verrucosa keratitis: a case report

et al. 2018

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BackgroundWe report a rare case of Phialophora verrucosa fungal keratitis, which required various types of treatment according to the intractable natural history of the disease.Case presentationA 51-year-old Thai man with poorly controlled diabetes received a bamboo branch injury and developed a perforated corneal lesion on his left eye. A pathological study from therapeutic penetrating keratoplasty showed fungal hyphae. This was later identified as Phialophora verrucosa by polymerase chain reaction. This organism was aggressive and recalcitrant because it relapsed with two corneal grafts and was resistant to amphotericin B, natamycin, and itraconazole. However, we found that the efficacy of voriconazole was promising for treating Phialophora verrucosa. We also used corneal cross-linking to establish corneal integrity after the infection was under control.ConclusionsBecause of the chronic nature of Phialophora verrucosa, a patient’s first visit may occur many years after trauma, and sometimes clinical presentation might not appear to indicate fungal infection. Therefore, a high index of suspicion is needed in this situation. Voriconazole showed good results in our case. Instead of using a more invasive keratoplasty, we used corneal cross-linking to strengthen the corneal biomechanics. To the best of our knowledge, this is the first case showing the benefit of corneal cross-linking to improve corneal biomechanics in resolved Phialophora verrucosa keratitis.

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“…This method exploits the property of riboflavin to generate, under UVA irradiation, reactive oxygen species that further interact with biological assemblies [ 5 ]. The CXL method is also applied for the treatment of other diseases associated with the extracellular matrix involving various veins [ 6 ], degraded dentine [ 7 ], or the eye (pellucid marginal corneal degeneration, post-LASIK ectasia, infectious keratitis, bullous keratopathy) [ 8 , 9 , 10 , 11 ]. Although numerous clinical trials involving patients with KC are dedicated to the analysis of the efficacy and effects of CXL, literature data are scarce on the physicochemical aspects behind this treatment.…”

Section: Introductionmentioning

confidence: 99%

Model Systems for Evidencing the Mediator Role of Riboflavin in the UVA Cross-Linking Treatment of Keratoconus

et al. 2021

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Riboflavin under UVA radiation generates reactive oxygen species (ROS) that can induce various changes in biological systems. Under controlled conditions, these processes can be used in some treatments for ocular or dermal diseases. For instance, corneal cross-linking (CXL) treatment of keratoconus involves UVA irradiation combined with riboflavin aiming to induce the formation of new collagen fibrils in cornea. To reduce the damaging effect of ROS formed in the presence of riboflavin and UVA, the CXL treatment is performed with the addition of polysaccharides (dextran). Hyaluronic acid is a polysaccharide that can be found in the aqueous layer of the tear film. In many cases, keratoconus patients also present dry eye syndrome that can be reduced by the application of topical solutions containing hyaluronic acid. This study presents physico-chemical evidence on the effect of riboflavin on collagen fibril formation revealed by the following methods: differential scanning microcalorimetry, rheology, and STEM images. The collagen used was extracted from calf skin that contains type I collagen similar to that found in the eye. Spin trapping experiments on collagen/hyaluronic acid/riboflavin solutions evidenced the formation of ROS species by electron paramagnetic resonance measurements.

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Keratoconus and Other Corneal Diseases: Pharmacologic Cross-Linking and Future Therapy

Cited by 5 publications

References 144 publications

Immobilization of Growth Factors for Cell Therapy Manufacturing

Immobilization of Growth Factors for Cell Therapy Manufacturing

Effectiveness of voriconazole and corneal cross-linking on Phialophora verrucosa keratitis: a case report

Model Systems for Evidencing the Mediator Role of Riboflavin in the UVA Cross-Linking Treatment of Keratoconus

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