The Network of Excellence in Corneal Regeneration

2014 Research Articles



Decellularized collagen matrix from tilapia fish scales for corneal reconstruction (BioCornea)

Hos D, van Essen TH, Bock F, Chou CH, Pan HA, Lin CC, Huang MC, Chen SC, Cursiefen C, Jager MJ.

Ophthalmologe. 2014 Nov;111(11):1027-32. doi: 10.1007/s00347-013-3011-y.


BACKGROUND: The worldwide need for donor corneal tissue clearly exceeds the availability of transplantable human tissue; therefore, recent efforts aim to identify and characterize alternative tissues, such as decellularized collagen scaffolds.

OBJECTIVES: The transparent fish scales of tilapia (Oreochromis mossambicus) were analyzed as a potential alternative for corneal reconstruction ("BioCornea").

MATERIAL AND METHODS: The article gives a review of the literature and own preliminary results. After decellularization the tissue characteristics of the fish scales, the repopulation with corneal epithelium and stromal cells, immunogenicity, the feasibility of corneal transplantation and the angiogenic properties were analyzed in vitro and in various animal models.

RESULTS: The fish scales mainly consist of collagen type I and show an architecture that is similar to the human cornea. Corneal epithelium and stromal cells are able to grow over and into the scaffold. It is possible to transplant fish scales in various animal models without severe inflammatory responses. Furthermore, in mice, less blood and lymphatic vessels grow into the xenograft when compared to conventional allogenic transplants.

CONCLUSION: Preliminary results with decellularized tilapia fish scales as an alternative for corneal reconstruction ("BioCornea") are promising.






Current treatment options with artificial corneas : Boston Kpro, Osteo-odontokeratoprosthesis, Miro Cornea® and KeraKlear®

Schrage N, Hille K, Cursiefen C.

Ophthalmologe. 2014 Nov;111(11):1010-8. doi: 10.1007/s00347-013-3009-5.


BACKGROUND: Although corneal transplant surgery in avascular normal risk eyes is becoming even more minimally invasive and successful, treatment options for difficult to treat patients with high risk eyes are still limited. In these cases HLA typed allogeneic transplants and artificial corneas (keratoprostheses) can be used.

METHODS: This article combines a review of the literature in PubMed and own clinical experiences on the use of artificial corneas in high risk eyes. Osteo-odontokeratoprosthesis (OOKP), Boston Kpro, Miro Cornea® and KeraKlear® corneas were used as clinical keratoprostheses.

RESULTS: Worldwide, the most experience exists for the use of Boston Kpro and OOKP in high risk eyes. Miro Cornea® and KeraKlear® are new procedures where only preliminary results are available and further evaluation is necessary. The longest experience and best anatomical long-term results have been achieved with OOKPs. Comparable cohorts are available for the Boston Kpro. The function of all keratoprostheses is threatened by secondary glaucoma. Implantation of the KeraKlear® prosthesis remains difficult. The Miro Cornea® shows an initially stable integration behavior.

CONCLUSION: Keratoprostheses, such as the Boston Kpro and OOKP are valid treatment options for eyes which are not open to therapy with allogeneic corneal transplantation. Modern implants such as KeraKlear® prosthesis and Miro Cornea® need further prospective clinical evaluation.






Results of a phase I/II clinical trial: standardized, non-xenogenic, cultivated limbal stem cell transplantation.

Zakaria N, Possemiers T, Dhubhghaill SN, Leysen I, Rozema J, Koppen C, Timmermans JP, Berneman Z, Tassignon MJ.

J Transl Med. 2014 Mar 3;12:58. doi: 10.1186/1479-5876-12-58.


BACKGROUND: To determine if a standardized, non-xenogenic, reduced manipulation cultivation and surgical transplantation of limbal stem cell grafts is a safe and effective treatment option for patients with total and partial limbal stem cell deficiency.

METHODS: In vitro cellular outgrowth and phenotype of the limbal epithelial cell and composite grafts were validated using a new protocol. Patients received either autologous (n = 15) or allogenic (n = 3) explants cultured using a standardized protocol free from xenogenic products. The resulting grafts were transplanted using a reduced manipulation surgical technique.

RESULTS: The majority of cells (>50%) displayed a progenitor phenotype typified by positive immunofluorescence for ∆Np63, CK14 and ABCG2 and low immunofluorescence for CK3/12 and desmoglein 3 proteins. The surgical protocol was designed to minimize manipulation and the graft itself was secured without sutures. The transplant recipients were followed for a mean of 24 months. Twelve of the 18 transplant recipients were graded as anatomically successful (67%), based on the defined success parameters. There was a significant reduction in corneal neovascularization, which was accompanied by an improvement in pain though not photophobia or central corneal opacity post transplant. The transplantation protocol showed no measureable effect on visual acuity.

CONCLUSION: We conclude that this standardized culture system and surgical approach is safe and effective in reducing corneal neovascularization. The technique is free from animal contaminants and maintains a large proportion of progenitor cells. Although this technique did not improve visual function, restoring a functional epithelial cell layer and reducing corneal neovascularization provides an improved platform for a penetrating keratoplasty to ultimately improve visual function.



See our media

The NExCR is managed by the COST (European Cooperation in Science and Technology)
Action BM1302 "Joining Forces in Corneal Regeneration Research" 2014-2017.