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Urocortin 2 (Ucn 2) is a CRF paralog that preferentially activates CRF2 receptors. Little is known regarding potential retinoprotective effects of Ucns despite the known presence of CRF family peptides and their receptors in retina. We investigated the effects of intravitreal Ucn 2 administration on ischemia-induced retinal degeneration (BCCAO). Two-month-old rats were subjected to BCCAO and their retinas were processed histologically after two weeks survival to determine the density of viable cells in the ganglionic cell layer and the thickness of all retinal layers. Immunohistological analysis of PKC-, calretinin-immunoreactivity was also performed. In BCCAO reduced retina thickness by approximately 60% as compared to sham-operated animals. Intraocular Ucn 2 treatment led to a nearly intact appearance of the retinal layers, and the thickness of all layers was signifi cantly increased by 40% compared to ischemic vehicle-treated subjects. Ucn 2 treatment also increased the number of cells by 55% in the ganglionic cell layer as compared to those from carotid-occluded retinas of vehicle-treated subjects. Ucn 2 also reversed the alterations found in the pattern of immunocytochemical markers, such as calretinin and PKC. These fi ndings suggest that intraocular Ucn 2 treatment may protect against ischemia-induced retinal degeneration, results with potential therapeutic implications for ophthalmic diseases. Support: OTKA: K72592; F67830; 78480; T061766; Richter.
Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophic and neuroprotective peptide that has been shown to exert protective effects in different neuronal injuries, models of neurodegenerative diseases and cerebral ischemia. PACAP and its receptors are present in the retina. PACAP is neuroprotective in several models of retinal degeneration in vitro and in vivo. In the present study we summarize the protective effects found with intravitreal PACAP treatment in the following models of retinal degeneration in rats: (1) toxic injury induced by monosodium glutamate (MSG) treatment; (2) ischemic injury (BCCAO) and (3) degeneration induced by different kind of UV-A light. MSG leads to the severe degeneration of the inner retinal layers. BCCAO cause degeneration in all retinal layers. UV-A exposure leads to a severe damage of the outer layers of the retina. In all cases, intravitreal PACAP injection (100 pmol) was administered into one (right) eye, while the other eye (left) received saline treatment, serving as control retinas. Histological and immunocytochemical analysis of the retinas showed that PACAP treatment signifi cantly ameliorated the damaging effects of all treatments. These results provide the basis for future clinical application of PACAP treatment in retinal degeneration. Support: OTKA: K72592; F67830; 78480; T061766; Gedeon Richter Ltd.
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