Systemic Administration of Bone Marrow Derived Mesenchymal Stem Cells limits/stabilizes the Development of Vascular Pathology in Rodent Retinal Degeneration Models

Abstract

Purpose: : Blinding ocular vascular pathology is associated with several disorders including retinopathy of prematurity, diabetic retinopathy and exudative macular degeneration. Our earlier study revealed that intravenous injection of bone marrow derived mesenchymal stem cells (MSCs) could limit pathological vascular changes in the Royal College of Surgeons (RCS) rat, a model for retinal degeneration. The present study is to investigate whether intravenous injection of MSCs at a later stage of retinal degeneration can limit/stabilize the development of vascular pathology observed in rodent models.

Methods: : MSCs were isolated from RCS rats and rd mice; 2millions of MSCs were injected intravenously into RCS rats (n=16) and rd mice (n=8) at postnatal (P) day 60, when the photoreceptors have lost 2/3 in the RCS rats and are nearly completely lost in rd mice; secondary vascular pathology has developed. Animals were examined 1-3 months later to determine vascular structure and visual function.

Results: : MSC injected animals showed a significant reduction in both vascular leakage and abnormal vascular complexes compared with controls (8-10 vs. 30-35 complexes). In addition, visual function, tested by optokinetic responses (OKR) and luminance threshold recording from the superior colliculus, were also preserved compared with age-matched untreated controls (p<0.01) in the RCS rats. Histological examination confirmed that there were 3-4 layers of preserved photoreceptors in MSC treated eyes, while in controls only a single layer of photoreceptors remained.

Conclusions: : This non-invasive MSC therapy, even when administrated at later stages of retinal degeneration, limits development of secondary vascular pathology, preserve vision and appears to stabilize the remaining vasculature. Understanding the mechanism of the vascular protection may lead to development of alternative therapies.

Keywords: retinal neovascularization • retinal degenerations: cell biology • transplantation