Bucolo, Claudio

Carnazza, Maria Luisa

Castorina, Alessandro

D'Agata, Velia

Drago, Filippo

Giunta, Salvatore

Firenze University Press: E-Journals

IJAE Vol. 115, n. 1/2 (Supplement), 2010
32
Expression of pituitary adenylate cyclase-activating 
peptide, vasoactive intestinal peptide and their 
receptors in diabetic rat retinas
Alessandro Castorina1, Salvatore Giunta1, Claudio Bucolo2, Maria Luisa Carnazza1, Filippo Drago2, 
Velia D’Agata1
1 Department of Anatomy, Diagnostic Pathology, Legal Medicine, Hygiene and Public Health, University of Catania, Italy
2 Department of Experimental and Clinical Pharmacology, University of Catania, Italy
Pituitary adenylate cyclase-activating peptide (PACAP), vasoactive intestinal pep-
tide (VIP) and their related receptors have already been described in the retina of dif-
ferent mammalian species during development. Based on relative affinity studies, at 
least three different binding sites have been identified for PACAP and VIP: the PACAP-
preferring PAC1 receptors and, VPAC1 and VPAC2 receptors which bind with equal 
affinity both PACAP and VIP. However, peptides and receptors expression in early dia-
betic retinopathy remains unknown. In the present study we investigated PACAP, VIP 
and relative receptors expression and distribution in the retina of streptozotocin (STZ)-
induced diabetic rats. 
Diabetes was induced in Wistar rats by a single STZ intraperitoneal injection. The ex-
pression of PACAP, VIP and receptors in healthy and early diabetic retinas were assayed 
both after 1 and 3 weeks by quantitative real-time PCR, Western blot and immunohis-
tochemical analyses. VPAC1 and VPAC2 receptors, as well as PACAP and VIP peptides 
mRNA levels were transiently induced by STZ-treatment within 1 week. After 3 weeks, 
PAC1, VPAC receptors and their related peptides expression levels were remarkably re-
duced in diabetic as compared to healthy rat retinas. These findings were confirmed at 
the protein level by immunoblot. Interestingly, immunohistochemical analyses revealed 
some peculiar changes in PACAP, VIP and receptors distribution between the two animal 
groups. In fact, after 1 week treatment, PACAP was more expressed in the retinal pigment-
ed epithelium (RPE) and in the inner segment of diabetic rats. Similarly, VIP reactivity 
was remarkably increased in the RPE, but also in the inner plexiform layer of STZ-treated 
rats. No apparent changes were observed in PAC1 immunoreactivity between healthy and 
diabetic rats, although the RPE was slightly less reactive in the latter group. VPAC2 recep-
tors seemed to be more expressed in the inner nuclear layer but less evident in the outer 
nuclear layer of STZ-treated rats. VPAC1 receptor retinal distribution was not affected by 
STZ-treatment. These differences were no longer observable 3 weeks after the STZ injec-
tion, although an overall reduction of both peptides and receptors expression occurred. 
In conclusion, this study provides evidence of an involvement of both PACAP and 
VIP peptides in early diabetic retinopathy. Furthermore, the overall downregulation of 
both peptides/receptors expression in retinas of STZ-treated rats after 3 weeks suggests 
that some deregulatory mechanisms might be activated in the later stages of retinal de-
generation. 
Key words
Streptozotocin, diabetes, retina, PACAP, VIP


Expression of pituitary adenylate cyclase-activating peptide, vasoactive intestinal peptide and their receptors in diabetic rat retinas

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Expression of pituitary adenylate cyclase-activating peptide, vasoactive intestinal peptide and their receptors in diabetic rat retinas

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