Prevalidation of a Human Cornea Construct as an Alternative to Animal Corneas for In Vitro Drug Absorption Studies

Development of an in vitro ocular test system for the prediction of all three GHS categories

“…Consequently, we previously generated a 3D cornea model based on human SV40-immortalized corneal cell lines Zorn-Kruppa et al, 2004Seeber et al, 2008;Manzer et al, 2009) which comprises both epithelium and stroma to provide an animal-free tool for eye irritation testing (Engelke et al, 2013) as well as for in vitro drug permeation studies (Hahne and Reichl, 2011;Hahne et al, 2012).…”

Cytochrome P450 Activity in Ex Vivo Cornea Models and a Human Cornea Construct

“…15 The permeation barrier equivalence of the HCC with ex vivo cornea models has been extensively demonstrated in drug absorption studies. 3,16 Moreover, similar expression patterns of several efflux drug transporter proteins have been demonstrated for the HCC compared with the human cornea. 17,18 However, in addition to passive diffusion and active drug transport, other factors, such as drug metabolism, may affect APIs during transcorneal passage.…”

“…In the case of passive diffusing APIs, the corneal thickness appears to be one crucial difference. 16 The rabbit cornea exhibits the thinnest cornea with a height of approximately 382 mm. 55 In contrast, the porcine cornea is approximately 666-mm thick, 56 resulting in lower permeation coefficients.…”

“Open Source”–Based Engineered Human Tissue Models: A New Gold Standard for Nonanimal Testing Through Openness, Transparency, and Collaboration, Promoted by the ALEXANDRA Association

“…4 Another example of OS-based tissue-engineered models was the development of the so-called Hemi-Cornea model, a 3D human corneal epithelial-stromal model composed of human cell lines. [22][23][24][25] This model was recently evaluated in a multicenter trial as a potential partial replacement method for in vivo eye irritation where each participating laboratory had to produce its own OS Hemi-Cornea models and consequently test 20 blinded compounds. Results were encouraging 26 and the organization of a regulatory validation study is currently under discussion (personal communications).…”