Abstract
ObjectiveThe vasodegenerative phase of diabetic retinopathy is characterized by not only retinal vascular degeneration but also inadequate vascular repair due to compromised bone marrow derived endothelial progenitor cells (EPCs). We propose that n-3 polyunsaturated fatty acid (PUFA) deficiency in diabetes results in activation of the central enzyme of sphingolipid metabolism, acid sphingomyelinase (ASM) and that ASM represents a molecular metabolic link connecting the initial damage in the retina and the dysfunction of EPCs.Research Design and MethodsType 2 diabetic rats on control or docosahexaenoic acid (DHA)-rich diet were studied. The number of acellular capillaries in the retinas was assessed by trypsin digest. mRNA levels of interleukin (IL)-1β, IL-6, intracellular adhesion molecule (ICAM)-1 in the retinas from diabetic animals were compared to controls and ASM protein was assessed by western analysis. EPCs were isolated from blood and bone marrow and their numbers and ability to form colonies in vitro, ASM activity and lipid profiles were determined.ResultsDHA-rich diet prevented diabetes-induced increase in the number of retinal acellular capillaries and significantly enhanced the life span of type 2 diabetic animals. DHA-rich diet blocked upregulation of ASM and other inflammatory markers in diabetic retina and prevented the increase in ASM activity in EPCs, normalized the numbers of circulating EPCs and improved EPC colony formation.ConclusionsIn a type 2 diabetes animal model, DHA-rich diet fully prevented retinal vascular pathology through inhibition of ASM in both retina and EPCs, leading to a concomitant suppression of retinal inflammation and correction of EPC number and function.
Highlights
In diabetes, dysfunction of the endothelium is a key factor in development of vascular complications [1], nonvascular retinal tissue plays an important role in the development of retinal pathology [2]
In this study of type 2 diabetes, we propose that n-3 polyunsaturated fatty acid (PUFA)-mediated acid sphingomyelinase (ASM) downregulation improves diabetic retinopathy outcomes through inhibition of retinal vascular damage and enhanced endothelial progenitor cells (EPCs) function leading to retinal vascular repair
To determine whether a docosahexaenoic acid (DHA) enriched diet has a protective effect against the development of retinal vascular pathology in type 2 diabetes, Bio-Breeding Zucker diabetic rats (BBZDR/Wor) and their age-matched non-diabetic BBDR littermates were used
Summary
Dysfunction of the endothelium is a key factor in development of vascular complications [1], nonvascular retinal tissue plays an important role in the development of retinal pathology [2]. During the vasodegenerative stage of diabetic retinopathy (DR), capillary components such as pericytes and endothelial cells die prematurely [3]. This diabetes-induced injury of the retinal microvessels leads to the hallmark features of DR: increased vascular permeability, acellular capillary formation and non-perfusion, and neovascularization in the proliferative stage of DR [3]. Our recent report revealed that diabetic bone marrow neuropathy affects EPC release and function and precedes retinal vascular degeneration in diabetes [8] providing additional evidence for the critical role of these cells in disease pathogenesis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
