Purchase this article with an account.
Hu Huang, Da'Kuawn Johnson, Dorothy Kim, Gerard Lutty; Blockade of PGF/VEGFR1 signaling significantly prevents BRB breakdown, apoptosis and inflammation in diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4633.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The goal of this study is to investigate the effects of blocking placental growth factor/vascular endothelia growth factor receptor 1 (PGF/VEGFR1) signaling on adverse complications in diabetic retinopathy (DR).
Placental growth factor knockout (PGFKO) mouse was crossed with the Ins2Akita (Akita) diabetic mouse to create the new Akita.PGFKO double mutant mouse strain. VEGFR1 activity in DR was blocked via neutralizing antibody (MF1). The integrity of blood-retinal barrier (BRB) was assessed by measuring vascular leakage into the retina using [3H]Mannitol as a tracer. Perfusion of retinal blood vessels was assessed by comparing the areas of perfused-dextran with GSA-lectin staining. Retinal capillary drop-out assays were performed on the isolated retinal microvasculature after elastase digestion. Cell apoptosis was determined by the activated Caspase-3 or TUNEL staining. Inflammation was investigated by counting the number of leukocyte adherent to the blood vessels (or retinal leukostasis). The expression of inflammatory and BRB makers was determined by real-time quantitative PCR and/or immunofluorescent staining.
Vascular leakage was significantly increased in Akita diabetic mice but was not in the Akita.PGFKO diabetic mice compared to their respective non-diabetic littermates. Retinal capillary degeneration was significantly increased in the Akita diabetic mice as compared with the wild type (WT) non-diabetic mice or the Akita.PGFKO diabetic mice. Apoptotic cell death was significantly increased in the Akita diabetic mice as compared with the Akita.PGFKO diabetic mice. Similarly, blockade of VEGFR1 by MF1 significantly inhibited diabetes-caused BRB breakdown, cell apoptosis and retinal leukostasis. Furthermore, in diabetic conditions, the expression of inflammatory markers, such as ICAM-1 and IL-1α were significantly suppressed by blockade of PGF/VEGFR1 signaling. In contrast, the expression of BRB markers, such as E-cadherin and ZO-1, were significantly elevated due to its blockade.
The results suggested PGF/VEGFR1 signaling is involved in the adverse complications during DR and is a potential target in the treatment of diabetes complications, such as diabetic macular edema.
This PDF is available to Subscribers Only