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PACAP promotes neuron survival in early experimental diabetic 4 retinopathy

Szabadfi, Krisztina and Szabó, Alíz and Kiss, Péter and Reglődi, Dóra and Sétáló, György and Kovács, Krisztina and Tamás, Andrea and Tóth, Gábor and Gábriel, Róbert (2014) PACAP promotes neuron survival in early experimental diabetic 4 retinopathy. Neurochemistry International, 64. pp. 84-91.

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Abstract

Metabolic changes induced by diabetes lead to a multifactorial progressive disease of the retina with an 33 extremely complex pathogenesis. One of the mechanisms of retinal cell death in diabetes is via apoptosis. 34 Our previous results show that pituitary adenylate cyclase activating polypeptide (PACAP) attenuates the 35 morphological and neurochemical changes in a rat model of diabetic retinopathy. The aim of this study 36 was to investigate the mechanisms of this protective effect. 37 Retinas of streptozotocin-induced diabetic rats were analyzed using apoptosis detection combined 38 with immunolabeling. Western blot was used to measure levels of pro- and anti-apoptotic pathways. 39 Intraocular PACAP injection markedly attenuated diabetic retinal injury: increased levels of the anti- 40 apoptotic p-Akt, p-ERK1, p-ERK2, PKC, Bcl-2, while decreased levels of the pro-apoptotic p-p38MAPK 41 and activated caspases (8, 3, 12) were detected. The number of apoptotic cells increased in all nuclear lay- 42 ers of diabetic retinas, but significantly decreased after PACAP treatment. Our results clearly demonstrate 43 that the protective effects of PACAP are mediated, at least partly, by attenuating apoptosis, including also 44 that of the dopaminergic amacrine cells. Inhibition of apoptosis is one of the PACAP-induced pathways 45 with therapeutic potential in early experimental diabetic retinopathy.

Item Type: Article
Subjects: R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
Depositing User: Prof Dóra Reglődi
Date Deposited: 06 Feb 2014 19:05
Last Modified: 08 Sep 2020 14:12
URI: http://real.mtak.hu/id/eprint/10074

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