Abstract
Purpose::
Diabetic retinopathy (DRP), the main cause for visual loss in adults, is associated with vascular proliferation, oedema and microthrombi. We hypothesized that microparticles (MP), submicron membrane vesicles released following cell activation or apoptosis, accumulate in vitreous fluid from patients with DRP.
Methods::
60 patients needing eye surgery were classed as non-diabetic (ND, n=26, 68±2 yrs) or diabetic (D, n=34, 60±2 yrs, 7.5±0.2% HbA1c, 28 with proliferative and 6 non-proliferative DRP). Levels and cellular origins of MP in platelet-free plasma and cell-free vitreous fluid were analyzed by flow cytometry, using annexinV (AnnV) labelling as a marker of apoptotic origin and specific markers for platelet (CD41) and endothelial (CD144) origins.
Results::
Plasma MP levels were not different in ND and D patients (1605±309 vs 1561±276 AnnV+MP/µl, 1265±254 vs 843±147 CD41+MP/µl, 198±45 vs 291±129 CD144+MP/µl, respectively). However vitreous MP levels were all markedly increased in D compared with ND patients (131±41 vs 54±24 AnnV+MP/µl, p=0.035; 94±25 vs 31±8 CD41+MP/µl, p=0.018; 197±38 vs 63±15 CD144+MP/µl, p<0.001, respectively). The ratio of vitreous to plasma MP levels indicates the importance of local formation versus potential plasma leakage of MP from microvessels in vitreous fluid. This ratio for CD144+MP was markedly greater than 1 in proliferative DRP (p=0.020), clearly indicating local accumulation of endothelial MP (Figure). For all markers the ratio was increased in proliferative DRP compared to ND.
Conclusions::
Proliferative DRP is associated with a specific ocular increase in MP shed from activated or apoptotic vascular endothelial cells.
Keywords: diabetic retinopathy • neovascularization • retinal neovascularization