Differential systemic gene expression profile in patients with diabetic macular edema: responders versus nonresponders to standard treatment.
BACKGROUND
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 profile helps us choose appropriate medicine, it would help customize treatment option for each patient. This forms the basis of our study.


METHODS
A case-control, prospective, observational series, where DME patients were treated with bevacizumab and subclassified as treatment naοve, treatment responders, and treatment nonresponders. Blood samples of 20 subjects were studied, with five patients in each of the groups (nondiabetic- group 1, treatment naοve- group 2, treatment responder- group 3, and treatment nonresponder-group 4). Whole blood RNA extraction followed by labeling, amplification and hybridization was done, and microarray data analyzed. Genes were classified 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 posttreatment. There were 19 genes upregulated and 8 genes downregulated in the inflammatory 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 inflammatory pathway. Seventeen genes were upreguated and 11 genes downregulated in receptor activity, which remained the predominant group in the group classification.


CONCLUSIONS
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 differential responses to treatment.
Department of Retina, Narayana Nethralaya, Bangalore, Karnataka, India.
Supriya S
SS
Dabir
Debashish
D
Das
Jeyabalan
J
Nallathambi
Shwetha
S
Mangalesh
Naresh Kumar
NK
Yadav
Jan S A G
JS
Schouten
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D016022:Case-Control Studies; D003930:Diabetic Retinopathy / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D017075:Laser Coagulation / Q000379:methods*; D008269:Macular Edema / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012313:RNA / Q000235:genetics*; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D014792:Visual Acuity
D020533:Angiogenesis Inhibitors; D012313:RNA