Abstract
Purpose: :
Diabetic Retinopathy is the leading cause of visual impairment in adults in the developed world. Increased vascular permeability and macular edema are key features of diabetic retinopathy. Pigment Epithelial Derived Factor (PEDF) has been shown to antagonize VEGF mediated vascular leakage. Human umbilical tissue-derived cells (hUTC) are allogeneic progenitor cells from human umbilical tissues that can secrete PEDF. The goal of this study is to assess efficacy of hUTC in vascular leakage in the rat diabetic model.
Methods: :
Diabetes was induced in Long Evans rats via single intraperitoneal administration of Streptozotocin. hUTC or vehicle control was given via subretinal injection 2 months after induction of diabetes. One month later vascular leakage was assessed with biotin-BSA assay. Expression of PEDF, VEGF, ICAM-1 and Zo-1 was assed by Western blots. Retinal thickness was analyzed by animal specific SD-OCT (Bioptigen)
Results: :
Subretinal Injection of hUTC lead to a significant reduction of vascular leakage compared to control (hUTC = 13.3 +/- 14.6, n=10, P<0.05 vs. control = 42 +/- 15.4, n=15 P<0.05). There was significant upregulation of PEDF expression, and inhibition of the diabetes induced ZO-1 downregulation, in the treated retinal tissues.
Conclusions: :
Subretinal injection of hUTC can reduce retinal vascular leakage in STZ induced diabetic rats and may become a novel therapeutic agent in patients with diabetic retinopathy.
Keywords: diabetic retinopathy • diabetes • retina