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Updated: Jun 21, 2026
Monitoring Dynamic Growth of Retinal Vessels in Oxygen-Induced Retinopathy Mouse Model
Published on: April 2, 2021
Increased hypoxia following vessel targeting in a murine model of retinoblastoma
Hinda Boutrid1, Yolanda Piña, Colleen M Cebulla
1Department of Ophthalmology, Bascom Palmer Eye Institute, Miami, FL 33101, USA.
Purpose:
The purpose of this study was to evaluate the effects of vessel targeting and chemotherapy agents on inducing hypoxic regions in LH(BETA)T(AG) murine retinal tumors. METHODS. Twelve- and 16-week-old LH(BETA)T(AG) transgenic retinoblastoma mice were treated with periocular injections to the right eye only of saline (n = 42), anecortave acetate (a single injection; 300 microg/20 microL; n = 42), or carboplatin (two injections per week for 3 weeks; 62.5 microg/20 microL; n = 42). Eyes were enucleated 1 day, 1 week, and 1 month after injection. To assess hypoxia, mice received 60 mg/kg pimonidazole via intraperitoneal injection. Eyes were enucleated, and tumor sections were analyzed.
Results:
Levels of hypoxia significantly increase in 16-week-old animals 1 day and 1 week after treatment with anecortave acetate, a known angiostatic agent. Eyes treated with anecortave acetate showed a 28% (P < 0.001) increase in hypoxic regions in comparison with the saline-treated control group 1 day after injection and a 17% (P < 0.001) increase 1 week after injection. In early tumors of 12-week-old animals, levels of hypoxia increased by 2.0% (P = 0.011) 1 day after anecortave acetate injection compared to controls. Levels of hypoxia significantly decrease in 16-week-old animals 1 week and 1 month after treatment with carboplatin, a chemotherapeutic agent. Eyes treated with carboplatin showed a 21.7% (P = 0.017) decrease in hypoxic regions in comparison with the saline-treated control group 1 week after injection and a 4.51% (P < 0.001) decrease 1 month after injection. In early tumors of 12-week-old animals, levels of hypoxia decreased by 0.0429% (P < 0.001) 1 month after carboplatin injection compared with controls.
Conclusions:
Treatment with a vessel-targeting agent results in changes in the tumor microenvironment as early as 1 day after treatment. By increasing hypoxia in tumors, vessel-targeting agents can be combined with glycolytic inhibitors which have been shown previously to target hypoxic regions in this transgenic model. This approach may have benefits for children with this disease and should be further investigated.
Insights
Vessel-targeting agents like anecortave acetate increase hypoxia in retinoblastoma tumors, while carboplatin decreases it. This suggests combining vessel-targeting agents with glycolytic inhibitors may benefit children with this disease.
Area of Science:
- Oncology
- Ophthalmology
- Translational Medicine
Background:
- Retinoblastoma is a pediatric eye cancer.
- Tumor hypoxia is a critical factor in retinoblastoma progression and treatment resistance.
- Understanding the impact of different therapeutic agents on tumor hypoxia is crucial for developing effective treatment strategies.
Purpose of the Study:
- To evaluate how vessel-targeting agents and chemotherapy affect hypoxic regions in LH(BETA)T(AG) murine retinoblastoma models.
- To assess the temporal changes in tumor hypoxia following treatment with anecortave acetate and carboplatin.
Main Methods:
- LH(BETA)T(AG) transgenic mice with retinoblastoma were treated with saline, anecortave acetate, or carboplatin.
- Pimonidazole was administered to assess hypoxia.
- Tumor sections were analyzed at 1 day, 1 week, and 1 month post-injection.
Main Results:
- Anecdotave acetate significantly increased hypoxia in 16-week-old mice (28% at 1 day, 17% at 1 week) and 12-week-old mice (2.0% at 1 day).
- Carboplatin significantly decreased hypoxia in 16-week-old mice (21.7% at 1 week, 4.51% at 1 month) and 12-week-old mice (0.0429% at 1 month).
- Vessel-targeting agents induced changes in the tumor microenvironment as early as 1 day post-treatment.
Conclusions:
- Vessel-targeting agents can increase tumor hypoxia, altering the tumor microenvironment.
- Combining vessel-targeting agents with glycolytic inhibitors could be a promising therapeutic strategy for retinoblastoma.
- Further investigation is warranted to explore this combination therapy for retinoblastoma treatment in children.
