Purchase this article with an account.
Filippo Drago, Alessandro Castorina, Salvatore Giunta, Marialuisa Carnazza, Velia D'Agata, Claudio Bucolo; Role of Pacap and Vip in STZ-induced Diabetic Rats. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5671.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To investigate the role of pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) and their receptors expression in the retina of streptozotocin (STZ)-induced diabetic rats.
Diabetes was induced in rats by a single injection of STZ (60 mg/kg, i.v.). Retinal expression of PACAP and VIP along with their receptors in control (non-diabetic) and diabetic animals were evaluated after 1 and 3 weeks by quantitative real-time PCR, Western blot and immunohistochemical analyses. Separate groups of diabetic rats were treated with PACAP (1pM/ µL; ITV) or vehicle as control, and Bcl2 and p53 expression were evaluated after 3 weeks from STZ injection. All the animals were treated according to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.
VPAC1 and VPAC2 receptors, as well as PACAP and VIP mRNA levels were transiently induced by STZ-treatment within 1 week. These findings were confirmed both by immunoblot and immunohistochemistry showing that no changes in receptors and peptides distribution occurred. Three weeks after treatment, levels of PAC1, VPAC receptors and peptides were remarkably reduced in diabetic retina compared to control. Further, STZ injection significantly downregulated the expression of the antiapoptotic gene Bcl2 and upregulated the expression of the proapoptotic effector p53, suggesting that diabetes promotes the activation of the intrinsic apoptotic pathway in retinas. Interestingly, this effect was partially counteracted by the single PACAP intravitreal injection, thereby causing a significant increase of Bcl2 gene expression and a significant reduction of p53 expression in comparison with vehicle-treated STZ rats.
The initial transient upregulation of PACAP and VIP and their receptors , and the subsequent downregulation in diabetic retinas suggest the activation of an endogenous PACAP- or VIP-mediated protective mechanism, probably through an autocrine/paracrine loop, which is not sufficient to counteract STZ-induced detrimental effects on retinas. Further, the present data seem to indicate that PACAP have beneficial effect in early experimental diabetic retinopathy and hold promise for clinical efficacy in patients.
This PDF is available to Subscribers Only