The advantages of a spontaneous, large animal model for FECD are numerous. First, naturally occurring diseases such as CED in BTs likely better reflect the complex environmental, genetic, and physiological variation present within the human population versus the highly uniform genetic background and homogenous environment characteristic of laboratory animals.
46 Second, dogs are commonly used to investigate corneal diseases
47,48 as well as for surgical interventions and outcomes especially with regard to keratoprosthetics
49 due to their similar corneal anatomy in comparison to humans, relatively large eyes, and ease of handling in the laboratory. Endothelial injury models have been described in the rabbit, primate, and cat using transcorneal freezing,
50,51 or surgical removal.
52 However, these models lack the ECM abnormalities intrinsic to FECD. The most well characterized FECD models are two a2 collagen VIII (
Col8a2) knock-in mouse models, which exhibit guttae and a decrease in endothelial cell density.
53,54 Both murine models have been used to investigate the therapeutic efficacy of lithium
55 and n-acetylcyteine.
56 However, the use of murine models are limited for novel pharmacologic, surgical, and cell-based interventions as well as gene therapy where a larger eye is more optimal to evaluate therapeutic efficacy.
46,57 Similarities in corneal thickness and structure suggest that pharmacokinetics would be more predictive for a canine versus murine model.
58,59 Thus, veterinary clinical trials of CED-affected patients may provide a relevant, predictive translational step in advancing novel FECD treatments from the benchtop to human clinical trials.
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