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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 New+Front+Ophthalmol
2016 ; 2
(5
): 192-204
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Genetic and epigenetic modifications in the pathogenesis of diabetic retinopathy:
a molecular link to regulate gene expression
#MMPMID28691104
Pradhan P
; Upadhyay N
; Tiwari A
; Singh LP
New Front Ophthalmol
2016[]; 2
(5
): 192-204
PMID28691104
show ga
Intensification in the frequency of diabetes and the associated vascular
complications has been a root cause of blindness and visual impairment worldwide.
One such vascular complication which has been the prominent cause of blindness;
retinal vasculature, neuronal and glial abnormalities is diabetic retinopathy
(DR), a chronic complicated outcome of Type 1 and Type 2 diabetes. It has also
become clear that "genetic" variations in population alone can't explain the
development and progression of diabetes and its complications including DR. DR
experiences engagement of foremost mediators of diabetes such as hyperglycemia,
oxidant stress, and inflammatory factors that lead to the dysregulation of
"epigenetic" mechanisms involving histone acetylation and histone and DNA
methylation, chromatin remodeling and expression of a complex set of
stress-regulated and disease-associated genes. In addition, both elevated glucose
concentration and insulin resistance leave a robust effect on epigenetic
reprogramming of the endothelial cells too, since endothelium associated with the
eye aids in maintaining the vascular homeostasis. Furthermore, several studies
conducted on the disease suggest that the modifications of the epigenome might be
the fundamental mechanism(s) for the proposed metabolic memory' resulting into
prolonged gene expression for inflammation and cellular dysfunction even after
attaining the glycemic control in diabetics. Henceforth, the present review
focuses on the aspects of genetic and epigenetic alterations in genes such as
vascular endothelial growth factor and aldose reductase considered being
associated with DR. In addition, we discuss briefly the role of the
thioredoxin-interacting protein TXNIP, which is strongly induced by high glucose
and diabetes, in cellular oxidative stress and mitochondrial dysfunction
potentially leading to chromatin remodeling and ocular complications of diabetes.
The identification of disease-associated genes and their epigenetic regulations
will lead to potential new drugs and gene therapies as well as personalized
medicine to prevent or slow down the progression of DR.