Retinal and ocular toxicity in ocular application of drugs and chemicals--part I: animal models and toxicity assays.
OBJECTIVE
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.
Penha
Fernando Marcondes
FM
Vision Institute, Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil. penhaepm@yahoo.com.br
Rodrigues
Eduardo B
EB
Maia
Maurício
M
Dib
Eduardo
E
Fiod Costa
Elaine
E
Furlani
Bruno A
BA
Nunes Moraes Filho
Milton
M
Dreyfuss
Juliana L
JL
Bottós
Juliana
J
Farah
Michel E
ME
D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D004596:Electroretinography / Q000187:drug effects; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D023421:Models, Animal; D012160:Retina / Q000187:drug effects*; D012164:Retinal Diseases / Q000139:chemically induced*; D018675:Toxicity Tests / Q000379:methods*