VIP

Vasoactive Intestinal Peptide
Vasoactive intestinal peptide (VIP) interacts with a widely expressed GPCR that stimulates AC/cAMP pathway. Similar to the enhanced REM seen in humans given intravenous (IV) VIP, animals show increased REM sleep following systemic, intraventricular, or brainstem VIP delivery; on the other hand, a VIP antagonist is REM suppressing.

Vasoactive intestinal peptide (VIP) is a 28-residue amino acid neuropeptide. It was first isolated and characterized in 1970 from porcine duodenum. Later it was found to be widely distributed in the central and peripheral nervous system. It was discovered owing to its potent vasodilatory effect leading to a short-lived decrease in mean arterial pressure. VIP exhibits a variety of applications in the area of ocular therapeutics. However, due to its inherent instability and lack of selectivity, the effects produced by this peptide are short lived and unpredictable. The recent progress of VIP-related medicine is aimed at improvement of its stability, selectivity, and efficacy with reduced adverse effects. In order to make optimal therapeutic use of VIP, it is essential to develop controlled and selective targeting formulations of VIP (Iwasaki et al., 2019; Séjourné et al., 1997). Research groups have developed intravitreal injection of VIP-encapsulated liposomes for the downregulation of endotoxin-induced uveitis (EIU). The developed liposomal system resulted in enhanced bioavailability and efficiency of VIP. A 24 h effect after formulation application and a 15 times higher concentration of VIP was achieved with liposomal formulation in comparison to saline/VIP injection. The clinical severity of EIU, ocular infiltrating polymorph nuclear leukocytes, and inflammatory cytokine and chemokine mRNA expression were significantly reduced (Lajavardi et al., 2007). Another study evaluated the benefits of a novel formulation of VIP based on the incorporation of VIP-loaded rhodamine-conjugated liposomes within hyaluronic acid gel for the treatment of EIU. The developed formulation was found to be an efficient strategy to obtain a sustained delivery of VIP in ocular and lymph node tissues (Lajavardi et al., 2009). Another study also investigated the effect of a single intravitreal injection of VIP loaded in rhodamine-conjugated liposomes on experimental autoimmune uveoretinitis (EAU). The developed formulation was found to reduce the macrophages expressed transforming growth factor-β2, levels of major histocompatibility complex class II, and nitric oxide synthase-2. T-cells showed activated caspase-3 with the preservation of photoreceptors. At the systemic level, treatment reduced retinal soluble autoantigen lymphocyte proliferation, decreased IL-2, and increased IL-10 in ILN cells, and diminished specific delayed-type hypersensitivity and serum concentration of IL-12 and IFN-γ. The encapsulation of VIP within liposomes was an effective strategy to deliver VIP into the eye for the prevention of EAU severity (Camelo et al., 2009).