Abstract
Diabetic retinopathy is the most common cause of legal blindness in developed countries at middle age adults. In this study diabetes was induced by streptozotocin (STZ) in male Wistar albino rats. After 3 months of diabetes, rights eye were injected intravitreally with green fluorescein protein (GFP) labelled bone marrow derived stem cells (BMSC) and left eyes with balanced salt solution (Sham). Animals were grouped as Baseline (n = 51), Diabetic (n = 45), Diabetic+BMSC (n = 45 eyes), Diabetic+Sham (n = 45 eyes), Healthy+BMSC (n = 6 eyes), Healthy+Sham (n = 6 eyes). Immunohistology analysis showed an increased retinal gliosis in the Diabetic group, compared to Baseline group, which was assessed with GFAP and vimentin expression. In the immunofluorescence analysis BMSC were observed to integrate mostly into the inner retina and expressing GFP. Diabetic group had prominently lower oscillatory potential wave amplitudes than the Baseline group. Three weeks after intravitreal injection Diabetic+BMSC group had significantly better amplitudes than the Diabetic+Sham group. Taken together intravitreal BMSC were thought to improve visual function.
Highlights
Diabetes, age-related macular degeneration and glaucoma are the most common causes of legal blindness in developed countries.[1]
[20] Intraocular transplantation of bone marrow derived stem cells (BMSC) can prevent retinal ganglion cell apoptosis in optic nerve injury or glaucoma models, [21, 22] and are shown to differentiate into photoreceptors in vivo and in vitro. [23]. To assess their possible functional effect in restoring vision, in this study, we evaluated the change in electroretinography (ERG) after intravitreal injection of rat BMSC in a streptozotocin (STZ) induced diabetes model; examined the migration of green fluorescein protein (GFP) labeled BMSC into the retina by immunofluorescence, assessed the degree of reactive gliosis in STZ induced diabetic retinopathy by immunohistochemistry with vimentin and glial fibrillary acidic protein (GFAP) antibodies, which was shown to be increased in diabetic retinopathy in previous studies, [24,25,26] and assessed any change in gliosis after intravitreal BMSC injection
The evaluation of GFAP expression in the healthy groups revealed that the Healthy+Sham group had a mean expression score of 1.33±0.58 (Fig 5E) and the Healthy+BMSC group 1.00 ±0 where the difference was insignificant (Fig 5F) (P>0.05)
Summary
Age-related macular degeneration and glaucoma are the most common causes of legal blindness in developed countries.[1] The common pathways in these conditions consist of the progressive loss of photoreceptors, interneurons, glial cells and ganglion cells. Despite of the prominent progress in ophthalmology, the World Health Organization estimated that diabetic retinopathy (DR) is responsible for 4.8% of the 37 million cases of blindness throughout the world. Some animals like amphibians have the capacity to PLOS ONE | DOI:10.1371/journal.pone.0156495. Streptozotocin Induced Diabetes and Stem Cells regenerate complete retina throughout their lives, [2, 3] mature mammalian eyes are thought to lack any retinal regenerative capacity. While promising, are still at early experimental stages in ophthalmology
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