A Role For Bone Marrow Cells In Angiogenesis: The Repopulation Of The Retina With Normal Vessels In A Model Of Oxygen Induced Retinopathy

Abstract

Purpose: : The retina is a very metabolically active tissue requiring a large amount of oxygen. Under hypoxic conditions, neovascularization occurs and can have severe negative repercussions on the retina. Retinopathy of prematurity (ROP), the leading cause of infant blindness, exemplifies the detrimental effects neovascularization can cause. These premature newborns acquire vaso-obliteration of micro vessels in the retina, followed by a pathological neovascularization once the retinal metabolic demand increases. In its most severe form ROP can lead to retinal detachment, potentially leading to blindness, or increased risk of myopia and other vision illnesses upon development. Oxygen induced retinopathy (OIR) is an animal model that replicates both phases of ROP and is achieved by exposing newborn mouse pups to 80% oxygen from post-natal day 7 to 12. There have been many advances in stem cell research regarding coronary and renal revascularization demonstrating a possible role for stem cells in angiogenesis. Utilizing bone marrow derived stem cells, we aimed to repopulate the retina with normal vessels which are affected in the OIR model.

Methods: : Two different cell types were isolated from mouse bone marrow: lineage negative (Lin-) and mesenchymal stem cells (MSC). Lin- cells contain hematopoietic stem cells and were isolated by depleting the bone marrow mononuclear cells of mature cell types. MSCs were isolated in culture according to their natural adherence quality. Both cell types were injected into the vitreous of mice having undergone the OIR model.

Results: : Mouse retinas collected at P17 from both MSC and Lin- injected mice demonstrated cell migration to the inner retina. Furthermore, MSC injected mice retinas showed reduced neovascularization and area of vaso-obliteration. Lin- injected retinas did not result in as significant healthy revascularization as the MSC injected retinas.

Conclusions: : Bone marrow derived stem cells migrate to the retina in mice having undergone the OIR model and promote proper vascular repair. MSCs are more efficient than lineage negative cells in increasing physiological vessel formation in the OIR model. These results suggest that MSCs play a role in angiogenesis and could have a therapeutic use in retinopathy of prematurity.

Keywords: retinopathy of prematurity • retinal neovascularization • hypoxia