Association of Plasma Semaphorin 3A With Phenotypes of Diabetic Retinopathy and Nephropathy

To investigate whether diabetic retinopathy phenotypes and albuminuria are associated with the overexpression of plasma semaphorin 3A (Sema3A). The study group with severe nonproliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR), the diabetes without diabetic retinopathy group, and the control group without diabetes consisted of all consecutive patients who were scheduled to undergo intravitreal bevacizumab injection for treatment-naïve diabetic macular edema (DME) and senile cataract surgery, respectively. In all subjects, the plasma Sema3A levels before intravitreal bevacizumab injections or cataract surgery were measured by enzyme-linked immunosorbent assay. In the patients with DME, the capillary nonperfusion area (measured by fluorescein angiography), total macular volume (measured by spectral-domain optical coherence tomography), and the urine albumin-to-creatinine ratio were determined. Severe NPDR (57 eyes) and PDR groups (51 eyes) both had significantly higher Sema3A levels than the control (58 eyes) and diabetes without diabetic retinopathy groups (54 eyes) (P < 0.001). Moreover, the PDR group had higher Sema3A levels than the severe NPDR group (P < 0.001). Plasma Sema3A levels correlated positively with the retinal nonperfusion area size (r = 0.844, P = 0.004), total macular volume (r = 0.765, P = 0.005), and the urine albumin-to-creatinine ratio (r = 0.752, P < 0.001). When DME patients were divided into normo-, micro-, and macroalbuminuria groups, the macroalbuminuria group had significantly higher plasma Sema3A levels than the microalbuminuria group or the normoalbuminuria group (P = 0.002 and P < 0.001, respectively). The plasma Sema3A levels correlated significantly with the phenotypes of diabetic retinopathy and albuminuria. This suggests that Sema3A may be a potential biomarker for diabetic retinopathy and nephropathy.