Anesztetikus prekondícionálás és a VIP/PACAP peptidcsalád védő szerepének vizsgálata iszkémiás retinopátiában

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is a widely distributed neuropeptide, first isolated from hypothalamic extracts. PACAP belongs to the vasoactive intestinal peptide (VIP)/secretin/glucagon peptide family. PACAP occurs throughout the nervous system and in peripheral organs. In the retina, PACAP immunoreactivity is present in the amacrine and horizontal cells, in the inner plexiform layer (IPL), in the ganglion cell layer (GCL), and in the nerve fiber layer (OFL). There are two types of PACAP receptors: PAC1 receptor, which binds PACAP with much higher affinity than VIP and VPAC1 and VPAC2 receptors, which bind VIP and PACAP with similar affinities. In the retina, the selective PAC1 receptor is predominant and its mRNA is present in the ganglion cells, amacrine cells and the inner nuclear layer (INL). The neurotrophic and neuroprotective effects of the peptide are now well established. PACAP protects neurons against different toxic agents in vitro and provides neuroprotection in several models of brain pathology. Among others, PACAP treatment results in smaller infarct size in focal cerebral ischemia, it leads to less extensive hippocampal damage in global cerebral ischemia, and it decreases postischemic endothelial dysfunction. PACAP is also protective in ischemic retinal lesions, in addition to the various other types of retinopathies in animal models, such as diabetic retinopathy, excitotoxic retinal injury, UV lightinduced degeneration, high intraocular pressure caused hypoperfusion, bilateral common carotid artery occlusion (BCCAO). Based on the important neurotrophic effects of PACAP during neuronal development, the involvement of the peptide in endogenous restorative processes was hypothesized. Several studies have demonstrated that endogenous PACAP increases upon nervous injury. Mice deficient in endogenous PACAP (PACAP KO) respond to insults with more severe deficits and lower level of regeneration, for example they have larger infarct size in models of stroke.