Potential Therapeutic Role of Pituitary Adenylate Cyclase-Activating Polypeptide for Dry Eye Disease

Abstract

Dry eye disease (DED) is caused by a reduction in the volume or quality of tears. The prevalence of DED is estimated to be 100 million in the developed world. As aging is a risk factor for DED, the prevalence of DED is expected to grow at a rapid pace in aging populations, thus creating an increased need for new therapies. This review summarizes DED medications currently in clinical use. Most current medications for DED focus on stimulating tear secretion, mucin secretion, or suppressing inflammation, rather than simply replenishing the ocular surface with moisture to improve symptoms. We recently reported that the neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) induces tear secretion and suppresses corneal injury caused by a reduction in tears. Moreover, it has been reported that a PACAP in water and a 0.9% saline solution at +4 °C showed high stability and achieved 80–90% effectiveness after 2 weeks of treatment. These results reveal PACAP as a candidate DED medication. Further research on the clinical applications of PACAP in DED is necessary.

Investigation of PACAP38 and PAC1 Receptor Expression in Human Retinoblastoma and the Effect of PACAP38 Administration on Human Y-79 Retinoblastoma Cells

“…Previous in vivo studies have confirmed that PACAP38, when administered as eye drops, can permeate ocular barriers and exhibit retinoprotective effects [76]. Additionally, PACAP38 has been identified as a new candidate medication for Dry Eye Disease [77]. A study suggests that VIP and PACAP analogs, explicitly developed for therapeutic purposes, can modulate molecular and cellular processes relevant to treating high-risk neuroblastoma [78].…”

Impact Assessment of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) and Hemostatic Sponge on Vascular Anastomosis Regeneration in Rats

“…For animal ethical reasons and to achieve the most accurate dosing possible, repeated needle administration was not used in our study, and we developed a cannulation method similar to Larsen and Christensen [54]. As the local administration of PACAP showed protective effects in a model of dry eye disease and in neurological animal models, local use is a preferred mode of treatment [55]. For instance, local administration of PACAP-38 has neuroprotective effects in animal models of ischemic stroke, traumatic brain injury, and Parkinson's disease [56,57].…”

Dry Eye Disease: An Update on Changing Perspectives on Causes, Diagnosis, and Management

“…Newer drugs, such as IL-1 receptor antagonists, serine protease inhibitors, resolvin analogues, and integrin antagonists, are under research [96]. The therapeutic role of pituitary adenylate cyclase-activating polypeptide is also being explored, and drug delivery systems, such as liposomal rebamipide, are being considered [97,98].…”