Insulin in the vitreous humor of patients with proliferative diabetic retinopathy

Abstract

Purpose : Initiation of intensive insulin therapy is a routine clinical practice for the management of patients with diabetes. However, this predisposes these patients to a marked increase in retinopathy risk, with initial worsening of retinopathy in the first two years. Presence of insulin in the vitreous humor of diabetic retinopathy (DR) patients may imply its pathological role in the development and progression of DR.

Methods : A total of 45 patients, scheduled for pars plana vitrectomy were categorised as per their pathologies under control (n = 12) and proliferative diabetic retinopathy (PDR) (n = 33) groups. The insulin and VEGF-A levels were estimated in both vitreous humor and plasma samples using Thermo Fisher Scientific, USA, ELISA kits. Whole genome SNP microarray (Affymetrix CytoScan HD; Affymetrix Inc., Santa Clara, USA) was performed on ten PDR patients to identify potential copy number changes (including gains and losses) and regions of homozygosity (ROH) using the ~750,000 SNP probes on this platform.

Results : Insulin was quantified in 11/33 patients in PDR group whereas no insulin was detected in control group. The vitreous humor VEGF levels were found to be significantly (p < 0.05) increased in the PDR group (1104.1 ± 1562.9) compared to control group (46.5 ± 109.3). The vitreous humor VEGF levels were higher in PDR group detected positive for insulin (PDRI) (1581.2 ± 1729.9) compared to PDR group detected negative for insulin (PDRN) (827.9 ± 1432.9). The vitreous humor VEGF levels were significantly (p < 0.05) increased in PDRI group (2810.3 ± 1775.7) compared to PDRN group (1022.6 ± 1563.4) in patients which did not receive intra-vitreal anti-VEGF within past 3 days from vitreous sampling. The VEGF levels were higher in PDRI group (557.0 ± 832.5) compared to PDRN group (130.5 ± 113.8) in patients which received intra-vitreal anti-VEGF within past 3 days from vitreous sampling. No findings of clincial significance were identified by the whole genome SNP microarray analysis.

Conclusions : The concordant presence of insulin and VEGF hints at the unknown underlying intracellular signalling cascade which could have clinical implication in these patients. The presence of insulin in the vitreous humor of these patients suggests a shift in the role of insulin from maintaining physiological homeostasis to being of pathological importance in the development and progression of PDR.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.