Abstract
Purpose: :
Diabetic retinopathy is proposed to involve endothelial cell damage due to low-grade chronic inflammation, which is further exacerbated by inadequate repair due to the compromised availability and functionality of bone marrow derived endothelial progenitor cells (EPCs). We previously demonstrated that bone marrow neuropathy preceded the decline of EPC in the blood and decreased viability of endothelial cells in a rat model of diabetic retinopathy. The purpose of this study was to directly test the hypothesis that bone marrow neuropathy leads to poor retinal vascular repair in diabetic retinopathy.
Methods: :
Surgical denervation of sciatic nerve in Male Sprague-Dawley rats was used as way to reproduce bone marrow pathology occurring in diabetes. Sham surgery was performed as a control. As accelerated model of non-proliferative diabetic retinopathy, a retinal ischemia-reperfusion (I/R) technique was then preformed on one eye of each animal. 48 hours after I/R, retinal vascular permeability was measured in animals by quantifying accumulation of FITC labeled albumin in the retina.
Results: :
We first compared permeability between the retina in I/R eye and the control eye, finding increased permeability in the I/R retina compared to uninjured eye. We found no statistically significant difference in retinal vascular permeability of uninjured eyes between rats with denervated bone marrow and sham controls. However, bone marrow denervation coupled with retinal ischemia resulted in a significant increase of vascular permeability in I/R retina of denervated animals as compared to I/R retina of sham controls, with an increase in permeability of more than 45%. We conclude that bone marrow denervation alone is not sufficient to produce retinal pathology however when coupled with vascular damage, lack of innervation leads to inadequate vascular repair and development of retinopathy.
Conclusions: :
This data supports our hypothesis that bone marrow neuropathy plays an important role in the diminished repair of retinal blood vessel by EPC. Improving our understanding of bone marrow pathology in diabetes could lead to the development of new drug targets and strategies to improve the outcome of diabetic retinopathy patients.
Keywords: diabetic retinopathy • innervation: neural regulation • ischemia