Platelets accumulate in the diabetic retinal vasculature following endothelial death and suppress blood-retinal barrier breakdown.
Platelet microthrombi are present in the diabetic retinal vasculature of humans and rodents; however, the mechanisms and consequences of their presence have not been defined. The current study demonstrates that platelet containing microthrombi accumulate in the retinal vasculature of the rat within 2 weeks of experimental diabetes, a timepoint at which leukocyte-mediated endothelial cell injury and death are known to occur. Platelet accumulation increased with the duration of diabetes, and crossover experiments revealed that maximal platelet accumulation required both diabetic platelets and a diabetic endothelium. Platelet accumulation also coincided with the expression of Fas and FasL in the diabetic retina. When endothelial cell apoptosis was inhibited with an anti-FasL neutralizing antibody, platelet accumulation was effectively suppressed. When platelets were depleted from the systemic circulation with an anti-platelet antibody, blood-retinal barrier breakdown worsened in the diabetic animals. These findings suggest that platelet accumulation in the diabetic retinal vasculature is secondary to endothelial cell death and serves, in part, to suppress blood-retinal barrier breakdown.
Yamashiro
Kenji
K
Angiogenesis/Retina Research Laboratory, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
Tsujikawa
Akitaka
A
Ishida
Susumu
S
Usui
Tomohiko
T
Kaji
Yuichi
Y
Honda
Yoshihito
Y
Ogura
Yuichiro
Y
Adamis
Anthony P
AP
D000818:Animals; D001792:Blood Platelets; D001813:Blood-Retinal Barrier / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D053222:Fas Ligand Protein; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology*; D013927:Thrombosis; D013997:Time Factors; D019014:fas Receptor / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D019014:fas Receptor