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Updated: Mar 15, 2026
Oxygen-Induced Retinopathy Model for Ischemic Retinal Diseases in Rodents
Published on: September 16, 2020
PACAP Is Protective in a Rat Model of Retinopathy of Prematurity
Timea Kvarik1,2, Barbara Mammel1,2, Dora Reglodi1
1Department of Anatomy, PTE-MTA "Lendulet" PACAP Research Team, University of Pecs, Pecs, Hungary.
Insights
Pituitary adenylate cyclase-activating polypeptide (PACAP) intravitreal treatment reduced avascular areas in a rat model of retinopathy of prematurity (ROP). This suggests PACAP may protect against ROP-related vascular changes.
Area of Science:
- Ophthalmology
- Developmental Biology
- Neuroscience
Background:
- Retinopathy of prematurity (ROP) is a leading cause of childhood visual impairment in preterm infants.
- Oxygen-induced retinopathy (OIR) is a standard rodent model for studying ROP.
- Pituitary adenylate cyclase-activating polypeptide (PACAP) exhibits known neuroprotective properties and is present in the retina.
Purpose of the Study:
- To investigate the potential of PACAP administration to mitigate vascular abnormalities in the rat OIR model.
- To assess the efficacy of both intraperitoneal and intravitreal PACAP delivery.
- To explore PACAP's influence on retinal vascular development and associated molecular changes.
Main Methods:
- Oxygen-induced retinopathy (OIR) was induced in rats by alternating oxygen concentrations from postnatal day 0 to 14.
- Animals received intraperitoneal or intravitreal PACAP or saline at specific postnatal days.
- Retinal vascularization was quantified on postnatal day 19 using isolectin staining, measuring avascular area and branching points.
- Cytokine expression was analyzed to understand molecular alterations.
Main Results:
- Intravitreal PACAP administration significantly reduced the avascular area in OIR retinas compared to controls.
- Intraperitoneal PACAP treatment did not show a significant effect on vascular extent.
- No significant changes in the number of vessel branching points were observed across treatment groups.
- PACAP treatment induced alterations in cytokine profiles, supporting its protective role.
Conclusions:
- Intravitreal PACAP effectively ameliorates vascular changes in a rodent model of ROP.
- PACAP demonstrates therapeutic potential for ROP, although the precise mechanisms require further elucidation.
- This study provides the first evidence of PACAP's beneficial effects in the context of ROP.
Abstract:
The oxygen-induced retinopathy (OIR) is a well-established rodent model of retinopathy of prematurity (ROP), which is one of the most common causes of childhood visual impairment affecting preterm babies. Pituitary adenylate cyclase-activating polypeptide (PACAP) is known to have neuroprotective effects. Several studies have revealed the presence of PACAP and its receptors in the retina and reported its protective effects in ischemic and diabetic retinopathy. In this study, we investigated whether PACAP administration can influence the vascular changes in the rat OIR model. OIR was generated by placing the animals in daily alternating 10/50 oxygen concentrations from postnatal day (PD) 0 to PD14 then returned them to room air. Meanwhile, animals received PACAP or saline intraperitoneally or intravitreally from PD1 to PD8 or on PD11, PD14, and PD17, respectively. On PD19 ± 1, the retinas were isolated and the vessels were visualized by isolectin staining. The percentage of avascular to whole retinal areas and the number of branching points were measured. Change in cytokine expression was also determined. Intravitreal treatment with PACAP remarkably reduced the extent of avascular area compared to the non- and saline-treated OIR groups. Intraperitoneal PACAP injection did not influence the vascular extent. Retinal images of room-air controls did not show vascular alterations. No changes in the number of vessel branching were observed after treatments. Alterations in cytokine profile after local PACAP injection further supported the protective role of the peptide. This is the first study to examine the effects of PACAP in ROP. Although the exact mechanism is still not revealed, the present results show that PACAP treatment can ameliorate the vascular changes in the animal model of ROP.
