PIWI-like protein, HIWI2: A novel player in proliferative diabetic retinopathy

Diabetic retinopathy (DR) is one of the major causes of blindness resulting from prolonged hyperglycemia which leads to breakdown of blood retinal barrier and excessive neovascularization. In our previous study, we demonstrated the presence of germline-specific PIWI-like proteins in human retina and retinal pigment epithelium (RPE) and a discrete function of HIWI2 (PIWIL4) in the assembly of tight junction through Akt/GSK3α/β. Recently, PIWI/piRNA has been suggested to be involved in the development of diabetes. Here, we have investigated the role of HIWI2 in proliferative diabetic retinopathy (PDR). Interestingly, Western blot analysis indicated the elevated expression of HIWI2 in vitreous aspirates of patients with PDR in comparison to macular hole (MH) and rhegmatogenous retinal detachment (RRD). In addition, treatment of ARPE19 with 25% of PDR vitreous aspirate significantly increased the expression of HIWI2. Moreover, exposure of ARPE19 to oxidative stress and VEGF, induced the expression of HIWI2. Further, we knocked down HIWI2 in ARPE19 cells to understand its role in the disease progression. Silencing HIWI2 reduced the expression of growth factors, VEGF and TGFβ1, and altered the expression of epithelial to mesenchymal transition (EMT) markers E-cadherin and αSMA. In addition, expression of MMP9 and cell migration was reduced in Si-HIWI2. Collectively, our report highlights a novel function and association of a piRNA binding protein, HIWI2 to PDR. The elevated expression of HIWI2 in PDR could influence various aspects of the disease pathogenesis, like EMT changes and cell migration. Hence, understanding the exact function of HIWI2 in retina could reveal its potential as a therapeutic target for retinopathy.