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 profile 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 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.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 differential responses to treatment.

Sustained intraocular VEGF neutralization results in retinal neurodegeneration in the Ins2Akita diabetic mouse

“…Nevertheless, our results show that sustained neutralization of VEGF in a pre-clinical model of type-1 diabetes promoted retinal neurodegeneration and induced vascular leakage. Although the proven benefit of anti-VEGF therapy in most DMO patients, a significant number of patients do not respond to the therapy 49 50 , suggesting that other factors may be fundamental in the pathogenesis of DMO in those non-responders. If this is indeed the case, our results suggest that the anti-VEGF therapy may potentially carry an “off-target” risk and the therapy may need to be applied more judiciously to avoid non-desirable side-effects.…”

Oxidative stress induces dysregulated autophagy in corneal epithelium of keratoconus patients

“…Total ribonucleic acid (RNA) extraction was performed on epithelial tissues and HCE cells by using the RNeasy Mini Kit (Qiagen) according to the manufacturer’s protocol and quantified using a nanodrop spectrophotometer (NanoDrop 1000, Thermo Scientific, DE, USA). Microarray and data analyses followed the protocols as described previously [ 24 ]. 1μg of the total RNA was converted to cDNA using the Biorad iScript™ cDNA Synthesis Kit.…”

Short Pulse of Clinical Concentration of Bevacizumab Modulates Human Retinal Pigment Epithelial Functionality

“…12,13 This necessitates investigating the cross-talk between anti-VEGFs and various signaling pathways. 14 Such studies could provide the basis for iovs.arvojournals.org j ISSN: 1552-5783 developing novel targeted therapies with minimal adverse effects.…”