A number of studies have proven that pituitary adenylate cyclase activating polypeptide
(PACAP) is protective in neurodegenerative diseases. Permanent bilateral common carotid
artery occlusion (BCCAO) causes severe degeneration in the rat retina. In our previous
studies, protective effects were observed with PACAP1-38, PACAP1-27, and VIP but not
with their related peptides, glucagon, or secretin in BCCAO. All three PACAP receptors
(PAC1, VPAC1, VPAC2) appear in the retina. Molecular and immunohistochemical analysis
demonstrated that the retinoprotective effects are most probably mainly mediated by
the PAC1 receptor. The aim of the present study was to investigate the retinoprotective
effects of a selective PAC1-receptor agonist maxadilan in BCCAO-induced retinopathy.
Wistar rats were used in the experiment. After performing BCCAO, the right eye was
treated with intravitreal maxadilan (0.1 or 1 muM), while the left eye was injected
with vehicle. Sham-operated rats received the same treatment. Two weeks after the
operation, retinas were processed for standard morphometric and molecular analysis.
Intravitreal injection of 0.1 or 1 muM maxadilan caused significant protection in
the thickness of most retinal layers and the number of cells in the GCL compared to
the BCCAO-operated eyes. In addition, 1 muM maxadilan application was more effective
than 0.1 muM maxadilan treatment in the ONL, INL, IPL, and the entire retina (OLM-ILM).
Maxadilan treatment significantly decreased cytokine expression (CINC-1, IL-1alpha,
and L-selectin) in ischemia. In summary, our histological and molecular analysis showed
that maxadilan, a selective PAC1 receptor agonist, has a protective role in BCCAO-induced
retinal degeneration, further supporting the role of PAC1 receptor conveying the retinoprotective
effects of PACAP.