Davunetide (NAP) protects the retina against early diabetic injury by reducing apoptotic death.
Davunetide (NAP) is an eight amino acid peptide that has been shown to provide potent neuroprotection. In the present study, we investigated the neuroprotective effect of NAP in diabetic retinopathy using an in vivo streptozotocin (STZ)-induced diabetic model. A single intraocular injection of NAP (100 μg/mL) or vehicle was administered 1 week after STZ injection. Three weeks after diabetes induction, we assessed the retinal expression and distribution of apoptosis markers, cleaved caspase-3, and Bcl2, by Western blot and immunofluorescent analysis. Furthermore, we evaluated the activation of mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) and/or phosphatidylinositol-3 kinase/Akt pathways by measuring the protein levels of p-ERK and p-AKT with or without NAP treatment. Results demonstrated that NAP treatment reduced apoptotic event in diabetic retina, and it restored cleaved caspase-3 expression levels in the retina of STZ-injected rats as well as the decreased Bcl2. NAP treatment improved cellular survival through the activation of the MAPK/ERK pathway. Taken together, these findings suggested that NAP might be useful to treat retinal degenerative diseases.
Department of Bio-Medical Sciences, Section of Anatomy and Histology, University of Catania, Via S. Sofia, 87, 95123, Catania, Italy.
Soraya
S
Scuderi
Agata Grazia
AG
D'Amico
Alessandro
A
Castorina
Concetta
C
Federico
Giuseppina
G
Marrazzo
Filippo
F
Drago
Claudio
C
Bucolo
Velia
V
D'Agata
D000818:Animals; D017209:Apoptosis; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000378:metabolism
D009842:Oligopeptides; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C425904:davunetide