Platelet-Derived Growth Factor-BB Generate Neural Stem Cells from Proliferating Retinal Astrocytes

Abstract

Abstract: : Purpose: In this study, we provide evidence that in the mouse retina, neural stem cells could be generated from proliferating retinal astrocytes, which have roles in the initiation and development of proliferative vitreoretinopathy (PVR). Methods: Retinal tissues were dissected from 3 month old C57BL/6J mice and subjected to organ culture incubation with 10 ng/ml of platelet derived growth factor-BB (PDGF-BB) for up to 2 weeks. 5-bromo-2’-deoxy-uridine (BrdU) was added to the cultures for the final 4 hours of incubation. Tissues were subjected to immunohistochemical studies using anti-BrdU and markers specific for neural stem cells, various retinal specific neurons, glial cells. Results: In response to PDGF-BB, astrocytes detached from the retinal tissues, proliferated, and formed extensive epiretinal cellular membranes. Furthermore, the proliferating astrocytes lost their glial acidic fibrillary protein (GFAP) expression and de-differentiated into neural stem cells. PDGF-BB also allowed proliferation of newly-generated neural stem cells via self-renewal, and caused differentiation of these newly-generated neural stem cells into retinal specific neurons, glial cells. Conclusions: Our data supports the hypothesis that proliferation and differentiation of neural stem cells, which could be derived from retinal astrocytes, is involved in epiretinal membrane formation in PVR.

Keywords: retinal culture • retinal glia • proliferative vitreoretinopathy