Abstract
Purpose:
Diabetic Retinopathy (DR) is the leading cause of acquired blindness and sight-threatening chronic micro vascular complication of diabetes mellitus. Dysfunction of mitochondria plays an important role both in the development of diabetes and DR. Therefore the aim of the study is to obtain the human retinal mitoscriptome gene expression signature for both DR and diabetes using human cadaver eyes.
Methods:
To identify retinal mitoscriptome genes that were differently expressed both in DR and diabetes, the RNA from the neural retinas of five postmortem donors without any history of retinal pathology, six patients retinas with a clinical features of DR and five retinas from diabetic donors without any signs of retinopathy were obtained for differential gene expression, by hybridization of labeled cRNA probes to an agilent human genome microarray 8*15k platform. Representative genes were validated by Taqman realtime quantitative PCR (qPCR).
Results:
In the microarray analysis, 59 genes were differentially expressed (p < 0.05) out of the 1100 genes in the DR as compared to normal control. Among those 59 genes, 8 showed an increased levels of expression (≥0.6), and 51 were expressed at decreased levels (≤0.6), in the retinas of DR patients compared to the control . In the diabetes 39 genes were differentially expressed (p<0.05) as compared to age matched control. In those 39 differentially expressed genes, 8 were up regulated and 31 were down regulated. In the DR retinas as compared to diabetic group 39 genes were shown differentially expression and among that 3 shows up regulation and 36 shows down regulation pattern. Focused qPCR results confirmed the differentially expressed genes both in DR and diabetes as compared to normal group.
Conclusions:
In this study, differentially expressed mitoscriptome genes pattern were observed for both in DR and diabetes which associates several new genes and pathways of disease mechanism. In the present study established human retinal mitoscriptome gene expression for both DR and diabetes to advance three related goals - Provide target for future biomarker development, Increase knowledge on mitochondrial involvement in the pathogenesis of DR and diabetes and Compare the similarity and difference of retinal mitoscriptome gene expression signature among normal and DR human cadaver eyes.