Mechanisms of Corneal Tissue Cross-linking in Response to Treatment with Topical Riboflavin and Long-Wavelength Ultraviolet Radiation (UVA)

McCall, A. Scott; Kraft, Stefan; Edelhauser, Henry F.; Kidder, George W.; Lundquist, Richard; Bradshaw, Helen E.; Dedeic, Zinaida; Dionne, Megan J. C.; Clement, Ethan M.; Conrad, Gary W.

doi:10.1167/iovs.09-3738

Cited by 254 publications

(246 citation statements)

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“…Cross-linking Treatment on Intact Whole Corneas ex VivoThe cross-linking procedure was performed as described previously (51). In brief, the bovine corneal epithelium was mechanically removed using a blunt knife, and riboflavin 0.1% (w/v) solution (RF ϩ PBS) was applied beginning 30 min before irradiation and continuing every 5 min during irradiation.…”

Section: Methodsmentioning

confidence: 99%

“…Currently, laboratory studies are mainly focused on documenting biomechanical effects (44), thermomechanical effects (45), morphological changes (46), effects on keratocytes (47), localization of cross-linking (48), and effects on collagenase resistance (49,50). However, the chemical mechanisms of collagen and PG interactions catalyzed by riboflavin ϩ UVA treatment during corneal cross-linking have not been elucidated except in recent work demonstrating that singlet oxygen and carbonyl groups are required (51). Some additional mechanisms are reported here.…”

mentioning

confidence: 99%

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Effects of Ultraviolet-A and Riboflavin on the Interaction of Collagen and Proteoglycans during Corneal Cross-linking

Zhang

Conrad

2011

Journal of Biological Chemistry

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161

112

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Corneal cross-linking using riboflavin and ultraviolet-A (RFUVA) is a clinical treatment targeting the stroma in progressive keratoconus. The stroma contains keratocan, lumican, mimecan, and decorin, core proteins of major proteoglycans (PGs) that bind collagen fibrils, playing important roles in stromal transparency. Here, a model reaction system using purified, non-glycosylated PG core proteins in solution in vitro has been compared with reactions inside an intact cornea, ex vivo, revealing effects of RFUVA on interactions between PGs and collagen cross-linking. Irradiation with UVA and riboflavin cross-links collagen ␣ and ␤ chains into larger polymers. In addition, RFUVA cross-links PG core proteins, forming higher molecular weight polymers. When collagen type I is mixed with individual purified, non-glycosylated PG core proteins in solution in vitro and subjected to RFUVA, both keratocan and lumican strongly inhibit collagen cross-linking. However, mimecan and decorin do not inhibit but instead form cross-links with collagen, forming new high molecular weight polymers. In contrast, corneal glycosaminoglycans, keratan sulfate and chondroitin sulfate, in isolation from their core proteins, are not cross-linked by RFUVA and do not form cross-links with collagen. Significantly, when RFUVA is conducted on intact corneas ex vivo, both keratocan and lumican, in their natively glycosylated form, do form cross-links with collagen. Thus, RFUVA causes cross-linking of collagen molecules among themselves and PG core proteins among themselves, together with limited linkages between collagen and keratocan, lumican, mimecan, and decorin. RFUVA as a diagnostic tool reveals that keratocan and lumican core proteins interact with collagen very differently than do mimecan and decorin.The cornea is the transparent, dome-shaped tissue covering the front of the eye. It is a powerful refracting surface, providing 65-75% of the eye's focusing power, and is made up of three distinct layers: epithelium, stroma, and endothelium. The stroma comprises about 90% of cornea thickness in humans (1).Although it is very highly innervated, it does not contain any blood vessels (2-4). Collagen gives the cornea its strength, elasticity, and form (5). The unique molecular shape, paracrystalline arrangement, and very regular fine diameter of the evenly spaced collagen fibrils are essential in producing a transparent cornea (6, 7).In the corneal stromal extracellular matrix, glycosaminoglycan (GAG) 2 polysaccharides are the most abundant negatively charged macromolecules and are classified on the basis of their repeating disaccharide structures into four main groups: keratan sulfate (KS), chondroitin sulfate/dermatan sulfate (CS/DS), heparan sulfate and heparin, and hyaluronan. Glycosaminoglycans, normally covalently attached to proteoglycan (PG) core proteins, play important roles in corneal transparency, nerve growth cone guidance, and cell adhesion, largely dependent on their patterns of sulfation or lack of it (8, 9). The corneal stroma is comp...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Effects of Ultraviolet-A and Riboflavin on the Interaction of Collagen and Proteoglycans during Corneal Cross-linking

Zhang

Conrad

2011

Journal of Biological Chemistry

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161

112

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“…It has proved its efficacy in arresting progression of keratoconus. [35][36][37] A limited number of studies and case reports have been published describing the effect of CXL in PMD. All showed improvement and/or stabilization of visual acuity and keratometric parameters.…”

Section: Collagen Cross-linkingmentioning

confidence: 99%

Treatment of Pellucid Marginal Degeneration

Farrag¹,

Hussein²,

Ummar³

2017

International Journal of Keratoconus and Ectatic Corneal Diseases

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Purpose: To summarize the recent trends in the treatment of pellucid marginal degeneration (PMD) based on available published data.Method and literature search: A PubMed search was conducted with combinations not limited to the following search terms: Pellucid marginal degeneration, Corneal ectasia, Corneal collagen cross-linking (CXL), Intracorneal ring segments (ICRS), Contact lens, Keratoplasty in corneal ectasia. A review of the search results was performed and relevant articles to the topic were included. Summary:Ophthalmologists have got a wide array of therapeutic modalities for the management of PMD. However, the key to optimal treatment is careful clinical assessment of patients and their visual requirements and tailoring the treatment to individual patients.

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“…sterilization, cell rinsing, freeze drying, etc. ); therefore these types of grafts are not viable in nature because their cellular structures are commonly destroyed during sterilization and other important tissue processing [72][73][74][75][76][77][78][79][80][81][82][83][84][85]. Therefore, it is a fact that the allo-and xenografts have significantly lower incorporative properties with the healing tissue and this is another major limitation which results in rapid absorption of the graft during tendon or ligament healing [69,72].…”

Section: Graft Options In Managing Large and Massive Tendon And Ligammentioning

confidence: 99%

“…This method of tissue engineering has been used for many years to decrease the antigenicity of the viable grafts [68][69][70][71][72]. Newer approaches have been developed by many and newer tissue engineered products are introduced in the recent years [73][74][75][76][77][78][79][80][81][82][83][84][85]. Basically, tissue engineering could be divided into four major categories including tissue scaffolds, healing promotive factors, stem cells and gene therapy [12].…”

Section: Tissue Engineeringmentioning

confidence: 99%

Tendon and Ligament Tissue Engineering, Healing and Regenerative Medicine

Moshiri¹,

Oryan²

2013

J Sports Med Doping Stud 2013

102

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Tendons transmit forces from muscle to bone and provide the joint function and ligaments transmit forces from bone to bone and provide joint stability. Tendon and ligament injuries have high incidence and management of tendon and ligament injuries is technically demanding because the healing response of these soft connective tissues is low. In addition, number of the available options to be considered as tissue replacement for large defects is low and healing of tendon and ligaments is faced to significant limitations. Among the available options, autografts are still gold standard but all the auto-allo and xenografts have their own limitations. Tissue engineering is a newer option but it is still primitive to be applicable extensively, in clinical setting. Tissue engineering could be divided into four categories including scaffolds, healing promotive factors, stem cells and gene therapy. To be able to have a good judgment regarding the management of tendon and ligament injuries, it is crucial to have a basic knowledge of tendon and ligament healing and regeneration. In this review, we discussed various types of tendon and ligament injuries and their incidence, and introduced the available and future options in managing large and massive tendon and ligament injuries. We specifically discussed the tissue engineering and it's advantageous and disadvantageous. To give a better clarification for the readers, we described different phases and cascades of tendon and ligament healing, modeling and remodeling, host-graft interaction after implantation of the graft and various types of prosthetic implants and finally provided some suggestions for the future investigations.

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Mechanisms of Corneal Tissue Cross-linking in Response to Treatment with Topical Riboflavin and Long-Wavelength Ultraviolet Radiation (UVA)

Cited by 254 publications

References 55 publications

Effects of Ultraviolet-A and Riboflavin on the Interaction of Collagen and Proteoglycans during Corneal Cross-linking

Effects of Ultraviolet-A and Riboflavin on the Interaction of Collagen and Proteoglycans during Corneal Cross-linking

Treatment of Pellucid Marginal Degeneration

Tendon and Ligament Tissue Engineering, Healing and Regenerative Medicine

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