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Updated: Aug 15, 2026
A Mouse Model for Laser-induced Choroidal Neovascularization
Published on: December 27, 2015
Periocular injection of microspheres containing PKC412 inhibits choroidal neovascularization in a porcine model
Yoshitsugu Saishin1, Raquel Lima Silva, Yumiko Saishin
1Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA.
Purpose:
Oral administration of PKC412, a kinase inhibitor that blocks several isoforms of protein kinase C (PKC) and receptors for vascular endothelial growth factor (VEGF), platelet-derived growth factor, and stem cell factor, inhibits ocular neovascularization in a murine model. The purpose of this study was to determine whether sustained local delivery of PKC412 in a human-sized eye inhibits choroidal neovascularization (CNV).
Methods:
Laser photocoagulation was used to rupture Bruch's membrane in young domestic pigs, and then a periocular injection of control microspheres or microspheres containing 25% or 50% PKC412 was given. After 10 days the integrated area of CNV at Bruch's membrane rupture sites was measured by image analysis. The levels of PKC412 in choroid, retina, and vitreous were measured either 10 or 20 days after periocular injection of 50% PKC microspheres or at 20 days after injection of 25% PKC412 microspheres.
Results:
The areas of CNV at Bruch's membrane rupture sites were significantly smaller in eyes that received a periocular injection of microspheres containing 25% (P=0.0042) or 50% (P=0.0012) PKC412 than those in eyes injected with control microspheres. Ten days after periocular injection of 50% PKC412 microspheres, PKC412 was detected in the choroid, but not in the retina or vitreous. Twenty days after periocular injection of 50% PKC412, high levels of PKC412 were measured in the choroid, vitreous, and retina. Levels were lower but still substantial in all three compartments 20 days after periocular injection of 25% microspheres.
Conclusions:
Sustained local delivery of PKC412 provides a promising approach for treatment of CNV.
Insights
Sustained local delivery of PKC412 microspheres significantly reduced choroidal neovascularization (CNV) in a large-animal model. This approach shows promise for treating CNV by inhibiting abnormal blood vessel growth in the eye.
Area of Science:
- Ophthalmology
- Pharmacology
- Biomedical Engineering
Background:
- Ocular neovascularization, including choroidal neovascularization (CNV), is a major cause of vision loss.
- Protein kinase C (PKC) inhibitors, such as PKC412, have shown potential in preclinical models.
- Developing effective and sustained delivery methods for ocular drugs is crucial for treating neovascular eye diseases.
Purpose of the Study:
- To evaluate the efficacy of sustained local delivery of PKC412 via microspheres in inhibiting choroidal neovascularization (CNV) in a human-sized eye model.
- To assess the drug distribution and persistence in ocular tissues following periocular injection.
Main Methods:
- A laser-induced rupture of Bruch's membrane model was used in young domestic pigs.
- Periocular injections of control or PKC412-loaded microspheres (25% or 50% concentration) were administered.
- Choroidal neovascularization area was quantified by image analysis, and drug levels in ocular tissues were measured over time.
Main Results:
- Periocular injection of PKC412 microspheres significantly reduced CNV areas compared to controls (P<0.005).
- PKC412 was detected in choroid, retina, and vitreous, with sustained levels observed up to 20 days post-injection.
- Higher concentrations of PKC412 led to greater drug presence in ocular tissues.
Conclusions:
- Sustained local delivery of PKC412 using microspheres is an effective strategy for inhibiting CNV.
- This localized delivery approach offers a promising therapeutic option for managing neovascular eye conditions.
- Further research into optimizing PKC412 delivery for clinical application in CNV is warranted.
