Differential systemic gene expression profile in patients with diabetic macular edema: Responders versus nonresponders to standard treatment.

ABSTRACT

Introduction: Diabetic macular edema (DME) is a vision-threatening complication of diabetic retinopathy. The current practice of management is a” trial and error “method of using intravitreal antivascular endothelial growth factor (VEGF)’’ or steroids to treat the patient and watch the response. However, if the patient’s genetic profi le helps us choose appropriate medicine, it would help customize treatment option for each patient. This forms the basis of our study. Materials and Methods: A case-control, prospective, observational series, where DME patients were treated with bevacizumab and subclassifi ed as treatment naïve, treatment responders, and treatment nonresponders. Blood samples of 20 subjects were studied, with fi ve patients in each of the groups (nondiabetic- group 1, treatment naïve- group 2, treatment responder- group 3, and treatment nonresponder-group 4). Whole blood RNA extraction followed by labeling, amplifi cation and hybridization was done, and microarray data analyzed. Genes were classifi ed based on functional category and pathways. Results: The total number of genes upregulated among all three experimental groups was 5, whereas 105 genes were downregulated. There were no common genes upregulated between the responders and nonresponders. There was only one gene upregulated between the diabetic and diabetic responders postt reatment. There were 19 genes upregulated and 8 genes downregulated in the infl ammatory pathway in group 2 versus group 1. There were no downregulated genes detected in vascular angiogenesis and transcription group. There were identical numbers of genes up- and downregulated in the infl ammatory pathway. Seventeen genes were upreguated and 11 genes downregulated in receptor activity, which remained the predominant group in the group classifi cation. Discussion: In summary, this study would provide an insight into the probable signaling mechanisms for disease pathogenesis as well as progression. This type of study eventually would aid in developing or improvising existing treatment modules with a rational approach towards personalized medicine, in future addressing the diff erential responses to treatment.