VEGF and PEDF levels in the rat retina: effects of aging and AMD-like retinopathy.

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly. By clinical signs, there are two forms of AMD: the atrophic or dry (~ 90% of all cases) and wet or neovascular AMD (~10% of cases). Anti-vascular endothelial growth factor (VEGF) intravitreal agents are the only successful treatment for wet AMD. However, there are emerging signals that anti-VEGF treatment can potentially increase development of atrophic AMD. There is neither a treatment of the dry AMD due poor understanding of the pathogenesis and retina aging process in general. We have shown previously that senescence-accelerated OXYS rats are a suitable model of dry AMD. Signs of retinopathy in OXYS rats manifest themselves by age 3 months against the background of a decline in the number of retinal pigment epithelium (RPE) cells and an alteration of choroidal microcirculation. Herein, we compared retinal expression of proteins VEGF and PEDF (pigment epithelium-derived factor) between OXYS and Wistar rats (control). The amount of the VEGF protein increased with age in the retina of both rat strains from 3 months of age. From age 3 to 24 months, this parameter was significantly lower in OXYS rats than in Wistar rats. PEDF protein concentration was significant lower in the OXYS retina only at the age of 3 months. We can conclude that development of retinopathy in OXYS rats takes place at reduced concentrations of VEGF and PEDF. Because RPE cells control the VEGF-PEDF balance, an RPE-targeted approach is a logical choice for AMD treatment and for decreasing adverse effects of anti-VEGF treatment.