Abstract
Purpose:
VEGF-A is a pivotal regulator of retinal neovascularization and a key pharmacological target for its prevention and cure. However, patients resistant to anti-VEGF therapies reveal the potential role of other contributing factors. The purpose of the present study was to determine the expression levels and immunolocalization of two VEGF-related growth factors: Prokineticin 1 (PKCN1), also known as eg-VEGF, and prokineticin 2 (PKCN2), also known as Bv8, which have been implicated in tumor angiogenesis and in induction of inflammatory processes.
Methods:
We assessed PKCN1 and 2 expression and localization in retinas of mice subjected to oxygen-induced retinopathy (OIR). Mice were exposed from postnatal day 7 to 12 (P7 and OIR12 respectively) to 73% oxygen tension. At OIR12 the mice were returned to normoxic conditions and analyzed at postnatal day 14 and 17 (OIR14 and OIR17, respectively). Western blotting, qRT-PCR and immunohistochemistry were employed to assess PKCN1 and 2 production and localization in the ischemic retinas and in age-matched control mice retinas (P12, P14 and P17).
Results:
Western blotting and immunohistochemical analyses revealed that PCKN1 and 2 were up-regulated in the ischemic retina (OIR14 and OIR17). Both of these factors appeared to be strongly co-localized with retinal and choroidal blood vessels. PCKN1- and 2-specific immunoreactivity was also evidenced in much less extent in the inner retina and around the retinal pigmented epithelium.
Conclusions:
Our data demonstrates the presence of PCKN1 and 2 in the developing retina and shows an induction in the expression of these VEGF-related proteins in the ischemic retina. The results of the present study, thus, suggest a potential role for these growth factors in the pathological processes associated with the induction and progression of ischemic retinopathy and retinal neovascularization.
Keywords: 748 vascular endothelial growth factor •
609 neovascularization •
688 retina