Deranged metabolic profile and identification of biomarkers in the vitreous humour of patients with proliferative diabetic retinopathy.

Systemic biochemical disarray has been implicated in the pathogenesis and progression of diabetes and its complications. The objective of the present study was to investigate the modifications in the metabolic state of the retina and its microenvironment in response to the systemic metabolic mal-function to understand the different pathways and biomarkers that may be involved in the patho-genesis and progression of proliferative diabetic retinopathy (PDR). The vitreous humour and plas-ma samples from 38 PDR, 7 proliferative vitreo retinopathy (PVR) and 17 control patients undergo-ing pars plana vitrectomy were analysed for sixteen different biomarkers. Whole genome single nu-cleotide polymorphism (SNP) microarray was performed on ten PDR patients' peripheral blood samples. The vitreous humour glucose, creatinine, micro protein, phosphorus and lactate dehydro-genase 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 pa-tients on insulin therapy and controls. SNPs previously associated with glucose (5), lactate dehy-drogenase (2) and creatinine (2) levels were identified to be polymorphic homozygous (minor allele) in ≥ 60% patients in this study, suggesting enhanced susceptibility. The metabolic overactivity of the retinal microenvironment appears to play a vital role in the pathogenesis of PDR. The signifi-cantly 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. The biochemical reference range of the vitreous humour in normal humans appears to have been reported for the first time.