Retinal and Ocular Toxicity in Ocular Application of Drugs and Chemicals – Part I: Animal Models and Toxicity Assays

Abstract

Aims: Experimental retinal research has gained great importance due to the ophthalmic pharmacotherapy era. An increasing number of drugs are constantly released into the market for the treatment of retinal diseases. In this review, animal species, animal models and toxicity assays in retinal research are discussed. Methods: An extensive search of the literature was performed to review various aspects of the methods of investigation of drug toxicity. The different types of animal species, as well as single animal models available for the evaluation of safety and efficacy of retinal pharmacotherapy, were identified. In addition, a large variety of reported laboratory techniques were critically examined. Results: In vitro studies are the first-line experiments for the development of a new drug for retinal diseases, using retinal pigment epithelial cells and other cell lines. The next step involves in vivo animal studies where nonhuman primates are considered the gold standard. However, cost and legal issues make their use difficult. Mice and rats provide genetically controlled models for investigations. Pigs, dogs and cats represent good large-size animal models, while rabbits are one of the most used species for retinal toxicity evaluations. Various laboratory methods were identified, including light microscopy, electron microscopy, electroretinography and new emerging methods, such as optical coherence tomography and scanning laser ophthalmoscopy for experimental purposes. Conclusions: A great number of animal species and models are available that simulate retinal diseases and provide experimental data for further human use. Work with animal models should include properly designed toxicity assays to obtain reliable results for safety and efficacy.

Examination of Kynurenine Toxicity on Corneal and Conjunctival Epithelium: In vitro and in vivo Studies

“…We adopted a rabbit model previously described by Moshirfar et al [21]. It is widely accepted that the rabbit cornea responds similarly to the human cornea in terms of timing, the extent of scarring, and myofibroblast formation, and it has been used in research for many years [17]. Rabbit cornea is also convenient because of its similarity to the human cornea in size and the typically used epithelium debridement size is 5 or 6 mm, which is easy to follow [18-21].…”

“…The in vivo studies were performed because animals are still important for drug toxicity assessment prior to human use [17]. We selected a corneal wound healing model in rabbits, which is widely used in pre-clinical studies of the potential toxicity of various compounds applied topically [17-20].…”

“…We selected a corneal wound healing model in rabbits, which is widely used in pre-clinical studies of the potential toxicity of various compounds applied topically [17-20]. …”

Biochemical Analysis and Decomposition Products of Indocyanine Green in Relation to Solvents, Dye Concentrations and Laser Exposure

“…Previous laboratory investigations have shown that various changes in pH from solutions applied to the retina may cause toxicity [27]. In the retina, pH changes were found to strongly affect the retinal component of the c-wave and b-wave in the perfused cat eye model [28].…”

Translational models of ocular disease

“…The rabbit is heavily used in safety and toxicity studies of ocular therapeutics and potential toxins . To study the latter, a growing repertoire of in vitro tests have been developed .…”