PACAP and its receptors in the retina of various species

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved neuropeptide with well-established neuroprotective actions in the central and peripheral nervous system. Owing to the developmental and functional relationship between the brain and the retina, growing attention has focused on the retinal distribution of PACAP and its receptors, as well as their potential translational relevance. The aim of the present review is to summarize occurrence and distribution of PACAP and its receptors in different vertebrate species. Comparative studies across vertebrates (including fish, birds, rodents, and primates) demonstrate a remarkably conserved retinal expression pattern, particularly for the PAC1 receptor. PACAP signaling components are predominantly localized to the inner retinal layers, with frequent expression in amacrine and bipolar cells and, in some species, Müller glia. Early embryonic expression observed in several species suggests roles in retinal neurogenesis, differentiation, and synaptic maturation, while persistent adult expression supports involvement in synaptic modulation, circadian regulation, and neuronal maintenance. Extensive experimental evidence from rodent models shows that PACAP exerts robust retinoprotective effects in excitotoxic, ischemic, diabetic, and glaucomatous injury paradigms. These protective actions are associated with modulation of pro-survival signaling pathways, attenuation of inflammatory responses, and reduction of apoptotic processes. Importantly, human retinal tissue exhibits comparable localization patterns, and in vitro studies in human-derived retinal cells confirm cytoprotective effects. The evolutionary conservation of retinal PACAP signaling underscores its fundamental physiological importance and supports further investigation of PACAP-based translational strategies for vision-threatening retinal disorders.