Pituitary Adenylate Cyclase Activating Polypeptide, A Potential Therapeutic Agent for Diabetic Retinopathy in Rats: Focus on the Vertical Information Processing Pathway
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- 作者：K. Szabadfi ; D. Reglodi ; A. Szabo ; B. Szalontai ; A. Valasek…
- 关键词：Retinal pigment epithelium ; Photoreceptors ; Bipolar cells ; Ganglion cells ; Ribbon synapses
- 刊名：Neurotoxicity Research
- 出版年：2016
- 出版时间：April 2016
- 年：2016
- 卷：29
- 期：3
- 页码：432-446
- 全文大小：4,955 KB
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D. Reglodi (2) (5)
A. Szabo (3)
B. Szalontai (1) (2)
A. Valasek (1) (2)
Gy. Setalo Jr. (4)
P. Kiss (5)
A. Tamas (5)
M. Wilhelm (6)
R. Gabriel (1) (2)
1. Departments of Experimental Zoology and Neurobiology, University of Pecs, Pecs, Hungary
2. Janos Szentagothai Research Centre, University of Pecs, Pecs, Hungary
5. Department of Anatomy, MTA-PTE PACAP Lendulet Research Group, University of Pecs, Szigeti u. 12., Pecs, 7624, Hungary
3. Biochemistry and Medical Chemistry, University of Pecs, Pecs, Hungary
4. Medical Biology, University of Pecs, Pecs, Hungary
6. Sport Sciences and Physical Education, University of Pecs, Pecs, Hungary - 刊物主题：Neurosciences; Neurology; Neurochemistry; Pharmacology/Toxicology; Neurobiology; Cell Biology;
- 出版者：Springer US
- ISSN：1476-3524
文摘
Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophic and neuroprotective peptide that has been shown to exert protective effects in different neuronal injuries, such as retinal degenerations. Diabetic retinopathy (DR), the most common complication of diabetes, affects the microvasculature and neuronal architecture of the retina. We have proven earlier that PACAP is also protective in a rat model of DR. In this study, streptozotocin-induced DR was treated with intravitreal PACAP administration in order to further analyze the synaptic structure and proteins of PACAP-treated diabetic retinas, primarily in the vertical information processing pathway. Streptozotocin-treated Wistar rats received intravitreal PACAP injection three times into the right eye 2 weeks after the induction of diabetes. Morphological and molecular biological (qRT-PCR; Western blot) methods were used to analyze retinal synapses (ribbons, conventional) and related structures. Electron microscopic analysis revealed that retinal pigment epithelium, the ribbon synapses and other synaptic profiles suffered alterations in diabetes. However, in PACAP-treated diabetic retinas more bipolar ribbon synapses were found intact in the inner plexiform layer than in DR animals. The ribbon synapse was marked with C-terminal binding protein 2/Bassoon and formed horseshoe-shape ribbons, which were more retained in PACAP-treated diabetic retinas than in DR rats. These results are supported by molecular biological data. The selective degeneration of related structures such as bipolar and ganglion cells could be ameliorated by PACAP treatment. In summary, intravitreal administration of PACAP may have therapeutic potential in streptozotocin-induced DR through maintaining synapse integrity in the vertical pathway.