The Genetic Study of Diabetic Retinopathy

Author: Sotoodeh Abhary

Abhary, Sotoodeh, 2012 The Genetic Study of Diabetic Retinopathy, Flinders University, School of Medicine

This electronic version is made publicly available by Flinders University in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material and/or you believe that any material has been made available without permission of the copyright owner please contact with the details.


Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus (DM). It is the fifth most common causes of blindness in the world, accounting for approximately 4.8% of global blindness and is also the leading cause of blindness in working age adults. The pathogenesis of DR is complex and multifactorial, but at a biochemical level is related to altered glucose metabolism. Established risk factors in the development of DR include prolonged hyperglycemia, increased duration of DM, uncontrolled hypertension and hyperlipidemia. It has become evident through familial aggregation studies that susceptibility to DR also has a heritable component, independent of other established risk factors. The aim of this thesis was to further explore genetic risk factors in the development of DR in type 1 DM and type 2 DM. A meta-analysis of all of the published candidate gene studies for DR has been undertaken and a total of 34 variants in 20 genes have been analysed, with 5 genes found to be significantly associated with DR. Six candidate gene studies have been undertaken, including replication studies of two of the genes associated with DR in the meta-analysis. In particular, variation in the vascular endothelial growth factor and erythropoietin gene were found to be significantly associated with DR, especially sight-threatening DR. A serum protein study investigating the nitric oxide pathway was undertaken and found asymmetric and symmetric dimethylarginines and L-arginine to be significantly associated with sight-threatening DR. Finally, a genome-wide association study was undertaken and identified several novel susceptibility genes for sight-threatening DR. This study advances understanding of DR pathogenesis, and may assist in refinement of genetic screening programs to identify individuals at particularly high risk of DR. Data from this study may also assist in the identification of novel therapeutic targets for DR.

Keywords: diabetic retinopathy,diabetes,genetic,genes
Subject: Ophthalmology thesis, Medicine thesis

Thesis type: Doctor of Philosophy
Completed: 2012
School: School of Medicine
Supervisor: Prof Jamie Craig