Title:Proliferative Retinopathies: Animal Models and Therapeutic Opportunities
Volume: 12
Issue: 2
Author(s): Pilar Villacampa, Virginia Haurigot and Fatima Bosch
Affiliation:
Keywords:
IGF-I, retinopathy, neovascularization, neurodegeneration, gliosis, VEGF, PEDF, AAV vectors.
Abstract: Proliferative retinopathies are the leading causes of blindness in Western societies. The development of new,
more efficacious treatments that take advantage of recent advances in the fields of gene and cell therapy requires further
investigations on the mechanisms underlying disease onset and progression, and adequate animal models that recapitulate
the pathogenesis of human proliferative retinopathy and allow evaluation of the long-term therapeutic benefits that these
therapies can offer. Unfortunately, most models of retinal neovascularization have short-term evolution and diabetic rodents
show a very mild retinal phenotype, limited to non-proliferative changes, and do not develop proliferative retinopathy
at all. Transgenic mice overexpressing Insulin-like Growth Factor-I (IGF-I) in the retina (TgIGF-I) constitute the only
rodent model currently available that develops most of the retinal alterations observed in diabetic eyes, with a temporal
evolution that resembles that of the human disease. TgIGF-I have retinal vascular alterations that progress as animals age
from non-proliferative to proliferative disease, making these mice an excellent model of proliferative retinopathy that, due
to its slow progression, allows long-term evaluation of novel antiangiogenic therapies. At the molecular level, transgenic
retinas recapitulate a variety of changes that are also observed in diabetic retinas, which reinforces the validity of this
model. In addition to vascular and glial alterations, Tg-IGF-I mice show progressive neurodegeneration that leads to
blindness in old animals. Thus, TgIGF-I are a useful model for testing the long-term efficacy and safety of innovative
antiangiogenic, glial-modulating and neuroprotective therapies for the treatment of diabetic retinopathy and other retinal
proliferative disorders.
