Screening Blood and Vitreous for Biomarkers Associated with Proliferative Diabetic Retinopathy.

: Uncontrolled or long-standing diabetes can lead to proliferative diabetic retinopathy (PDR), a condition that significantly impairs vision. A subset of patients does not respond adequately to conventional therapies, such as intravitreal injections of anti-vascular endothelial growth factor (VEGF) or laser treatment. This study aims to identify potential biomarkers for alternative treatment pathways in the vitreous and blood of patients with severe PDR. : Vitreous samples were collected from PDR patients ( = 3) undergoing vitrectomy for vitreous hemorrhage and from control patients ( = 9) undergoing ocular surgery for epiretinal membrane or macular holes. Blood samples were collected from a separate group of PDR patients ( = 13) and non-diabetic control patients without retinopathy ( = 13). Medical histories were obtained. Two-stage real-time quantitative polymerase chain reaction (qPCR) was used to evaluate mRNA expression levels of genes potentially implicated in PDR, including , , , , , and . Molecular and statistical analyses were performed to compare PDR and control vitreous and blood samples. : The PDR vitrectomy group included two females and one male, aged 71-77 years (mean 74 years). All participants had undergone pan-retinal photocoagulation and two had received anti-VEGF injections before vitrectomy. These participants had elevated HbA1c levels. Targeted vitreous gene analysis revealed varying levels of increased expression of all genes examined as compared to the control group. A trend for increased median expression was demonstrated for all examined genes: by 1.44-fold (PDR = 2.50, control = 1.74, = 0.21), by 1.56-fold (PDR = 3.00, control = 1.93, = 0.37), by 1.36-fold (PDR = 2.33, control = 1.72, = 0.66), by 2.06-fold (PDR = 2.81, control = 1.36, = 0.51), by 2.93-fold (PDR = 6.32, control = 2.16, = 0.1), and by 3.53-fold (PDR = 3.51, control = 0.99, = 0.08). PDR blood sample analysis as compared to controls showed a trend for increased expression of by 1.2-fold (PDR = 0.88, control = 0.74, = 0.57), whereas the other examined genes showed a trend of reduced expression; decreased by 0.50-fold (PDR = 0.38, control = 0.75, = 0.07), by 0.51-fold (PDR = 0.35, control = 0.69, = 0.09), by 0.79-fold (PDR = 0.79, control = 1.00, = 0.54), by 0.70-fold (PDR = 0.58, control = 0.82, = 0.34), and by 0.45-fold (PDR = 0.51, control = 1.15, = 0.11). : Vitreous sample analysis revealed a trend of increased mRNA expression of and in patients with PDR. Blood sample analysis did not show a significant increase of mRNA expression but a decreased trend of , , and mRNA expression. These trends warrant validation in a larger cohort to explore alternative pathways for targeted treatment.