Neuroprotection by endothelial progenitor cells for retinal degeneration

Abstract

Retinitis pigmentosa is an inherited eye disorder that leads to profound vision loss and is characterized by retinal neuron degeneration, fundus pigment changes, optic disc atrophy, and vasculature attenuation. Endothelial progenitor cells (EPCs), which contribute to angiogenesis, are categorized into two subpopulations according to their aldehyde dehydrogenase (ALDH) activity. Injection of EPCs with low ALDH activity (Alde-Low) revealed a greater ability for neuroprotection and vasoprotection compared with injection of EPCs with high ALDH activity in a mouse model of retinitis pigmentosa. However, EPCs do not possess direct neuroprotective or vasoprotective ability and must recruit other neuroprotective and vasoprotective cells. Alde-Low EPCs selectively recruited neuroprotective and vasoprotective F4/80+/Ly6c+ monocyte-derived macrophages from bone marrow through CCL2 secretion. F4/80+/Ly6c+ monocyte-derived macrophages from bone marrow were immature and revealed characteristics that differed from those of retinal residual microglia. CCR2 (the receptor for CCL2), neurotrophic factors, and anti-inflammatory mediators were highly expressed in migrated F4/80+/Ly6c+ monocyte-derived macrophages when compared with retinal residual microglia. These new findings suggest that novel therapies using EPCs may delay the progression of retinal degeneration.