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Elva Hortencia Adan-Castro, Nundehui Diaz-Lezama, Gonzalo Martínez de la Escalera, Stephanie Thebault, Yazmín Macotela, Carmen Clapp; Analysis of retinal vasoinhibins and their ocular generation in diabetic and non-diabetic rats. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1053.
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Vasoinhibins are a family of antiangiogenic peptides derived from prolactin (PRL) by proteolytic cleavage. Given that vasoinhibins are present in the retina and that retinal angiogenesis determines diabetic retinopathy, we hypothesized that a down regulation of retinal vasoinhibins contributes to the progression of diabetic retinopathy. We therefore compared the levels of vasoinhibins and the activity of PRL-cleaving enzymes in the retina of diabetic and non-diabetic rats.
Vasoinhibins were evaluated by Western blot in the retina of non-diabetic rats and of diabetic rats treated four weeks earlier with a single injection of streptozotocin. To evaluate the activity of ocular proteases generating vasoinhibins from PRL, recombinant PRL was injected intravitreally into the eyes of rats, and vasoinhibins in the vitreous were determined at different time points by Western blot.
Higher levels of vasoinhibins were detected in the retina of diabetic rats relative to non-diabetic counterparts. PRL injected intravitreally was partially converted to vasoinhibins at 2 and up to 24 hours following injection. Both PRL and the resulting vasoinhibins were cleared over time, and such elimination was more rapid in eyes from diabetic rats.
These findings suggest that the diabetic condition associates with the upregulation of ocular proteases able to generate but also degrade vasoinhibins. The balance between these proteolytic actions may stabilize the levels of retinal vasoinhibins to help counteract pathological angiogenesis in diabetic retinopathy.
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