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From the Angiogenesis/Retina Research Laboratory,* Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts; the Department of Ophthalmology and Visual Sciences,
Kyoto University Graduate School of Medicine, Kyoto, Japan; the Department of Ophthalmology,
Keio University School of Medicine, Tokyo, Japan; the Department of Ophthalmology,
Faculty of Medicine, University of Tokyo, Tokyo, Japan; the Department of Ophthalmology,¶ Nagoya City University Medical School, Nagoya, Japan; and Eyetech Research Center,|| Woburn, Massachusetts
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.
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