Project Details
Projekt
Development, characterization and application of modified keratin and collagen matrices for corneal and conjunctival surface reconstruction
Subject Area
Ophthalmology
Term
from 2009 to 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 111595154
Severe ocular surface scarring can be found in many ocular surface disorders such as ocular mucous membrane pemphigoid, Stevens- Johnson syndrome and chemical/thermal burns. Fornix shortening, symblepharon and finally ankyloblepharon formation can be the clinical consequence. The cicatrisation of the fornices, especially the inferior fornix, causes entropion and trichiasis, which continually damages the ocular surface epithelia and results in recurrent erosions of the cornea, ulcer formation and secondary bacterial infection. Also, disturbed integrity of the tear film and dry eye symptoms can occur due to ineffective blinking, reduction of the tear meniscus, loss of goblet cells and keratinisation of the ocular surface epithelia. The resulting prolonged inflammation leads to destruction of limbal corneal stem cells and coverage of the cornea by conjunctival epithelial cells resulting in neovascularisation, ingrowth of fibrous tissue, chronic inflammation and stromal scarring leading to complete corneal opacification, severe pain and blindness. In these patients, reconstruction of the conjunctiva and the corneal surface have to be performed, especially in cases with total surface involvement, as attempts at corneal reconstruction alone will fail unless a conjunctival surface supporting the tear film is restored. The functions of the cornea and conjunctiva are complex and therefore a substitute tissue needs to meet several criteria. The first funding period of this project successfully established the usefulness of keratin based matrices for corneal surface reconstruction in vitro and in vivo as well as the successful use of plastic compressed collagen matrices as a matrix for conjunctival replacement. The aim of this follow-up project is to further improve these constructs for corneal and conjunctival replacement to specifically address certain clinical problems in ocular surface reconstruction, namely, persistent epithelial defects, as well as corneal neovascularization and scarring. For this purpose, strategies are being developed to embed the substances dexamethasone, NGF and bevacizumab, already studied active compounds for these indications, into both matrices and to provide them in therapeutically active concentrations on the ocular surface after implantation. First, various approaches of incorporation of the active substances are investigated as well as their impact on the biomechanical and optical properties of the matrices. A sustained release of substances from colloidal carrier systems (PLGA nanoparticles) and hydrogels is to be achieved after incorporation into the matrices. Of central importance is the development of an in-vivo near in-vitro method for determining the release of active substances from the matrices. In addition, the effect of modified matrices on corneal and conjunctival cell culture models will be studied and their usefulness will be finally assessed using an in vivo animal model.
DFG Programme
Research Grants
