Towards a blood test for diabetic retinopathy

Purpose Diabetic retinopathy (DR) is the leading cause of blindness among adults of working age in the UK. Early detection and appropriate management can prevent severe visual loss in 95% of cases. However, current screening methods are costly and suffer from subjective grading. Nucleic acids have been shown to circulate in plasma, with levels raised in conditions of cell death such as cancer and trauma. This study aimed to quantify circulatory retinal‐specific nucleic acids, and to evaluate potential for their use in the assessment of DR. Methods Diabetic patients (n = 106) and healthy controls (n = 24) were recruited from the Diabetes and Ophthalmology departments at St Thomas’ Hospital. RNA was extracted from whole blood, with quantitative real‐time RT‐PCR used to quantify mRNA levels for rhodopsin and RPE65, two proteins expressed exclusively in the retina. Beta‐actin mRNA was used for normalisation. Results Rhodopsin, RPE65 and beta‐actin mRNA were detected in 100% of subjects. Circulating rhodopsin and RPE65 mRNA levels were higher in diabetic patients than healthy individuals (p < 0.02). Circulating rhodopsin mRNA was raised in all DR groups compared to healthy individuals, irrespective of presence or severity of DR (p < 0.02). With respect to healthy controls, circulating RPE65 mRNA levels were higher in diabetic patients with background and proliferative DR (p < 0.02). Patients with active proliferative DR (neovascularisation, vitreous and pre‐retinal haemorrhage, or retinal detachment) possessed higher RPE65 mRNA and lower rhodopsin mRNA levels than those with quiescent disease (p < 0.01). Conclusion There is significant potential for use of these markers to screen for the presence of DR in diabetic patients in a quantitative manner using a blood test.