Deranged Metabolic Profile and Identification of Biomarkers in the Vitreous Humour of Patients with Proliferative Diabetic Retinopathy

Background: Systemic biochemical disarray has been implicated in the pathogenesis and progression of diabetes and its complications. However, the modifications in the metabolic state of the retina and its microenvironment in response to the systemic metabolic malfunction has not been documented.

Objective: The objective of the present study was to document the various biomarkers that may be involved in the pathogenesis and progression of Proliferative Diabetic Retinopathy (PDR).

Method: The vitreous humour and plasma samples from 38 PDR, 7 Proliferative Vitreo Retinopathy (PVR) and 17 control patients undergoing pars plana vitrectomy were analysed for sixteen different biomarkers. Whole genome Single Nucleotide Polymorphism (SNP) microarray was performed on ten PDR patients' peripheral blood samples.

Results: The vitreous humour glucose, creatinine, micro protein, phosphorus and lactate dehydrogenase were found significantly increased in the PDR patients compared to controls. The plasma urea, creatinine and micro protein were also significantly increased. The plasma phosphorus of PDR patients on oral hypoglycemic therapy was found significantly decreased compared with PDR patients on insulin therapy and controls. SNPs previously associated with glucose (5), lactate dehydrogenase (2) and creatinine (2) levels were identified to be polymorphic homozygous (minor allele) in ≥ 60% patients in this study, suggesting enhanced susceptibility.

Conclusion: The metabolic overactivity of the retinal microenvironment appears to play a vital role in the pathogenesis of PDR. The significantly elevated biomarkers may have diagnostic, prognostic and therapeutic significance. These findings shed light on the biochemical disarray in the vitreous humour of PDR patients that could have significant management implications.