A Novel Agent in Prevention of Acute Radiation Toxicity in the Mouse Retina

Abstract

Purpose : Although radiation retinopathy is a well-recognized entity, preventive measures have not been defined. We aimed to study how a novel agent, JP4-039, may prevent acute radiation toxicity in the mouse retina by stabilizing mitochondria and preventing apoptosis after irradiation.

Methods : Forty-five BALB/c mice were sorted into three groups of 15 mice each. Anesthesia was then performed on all mice with 2% isoflurane. Mice in Groups 1 and 2 received a 32-gauge/10 microliter intravitreal injection of either 40 nanogram JP4-039 (n=5 per group) or 30% cyclodextrin (control; n=5 per group). The remaining 5 mice in either group did not receive an intravitreal injection. Group 3 mice (n=15) all received an injection of BODIPY-labeled JP4-039. Thirty minutes after injection and further anesthesia with Nembutal, all mice in Groups 1 and 2 were irradiated with a dose of 18 Gy via 6 MV photon beam (Varian TrueBeaM^TM STx linear accelerator), while Group 3 mice remained without irradiation. All mice were then sacrificed and enucleated according to the following sequence: Group 1 and Group 2 underwent TUNEL assay 24 hours after irradiation to determine rate of apoptosis, or flow cytometry 120 hours after irradiation in order to detect retinal migration of inflammatory cells. Group 3 underwent fluorescent microscopy at 0, 15, 30, and 60 minutes after injection only, in order to determine retinal uptake of intravitreal JP4-039.

Results : Eyes treated with JP4-039 prior to irradiation had lower levels of retinal apoptosis (35.8 ± 2.5%) compared to controls (49.0 ± 2.7%; p=0.0066), as well as reduced migration of apoptotic N1 cells (30.7 ± 11.7%) compared to controls (77.7 ± 5.3%; p=0.0105). Retinal uptake of intravitreal JP4-039 was detected in the mouse retina 15, 30, and 60 minutes after injection.

Conclusions : Intravitreal injection of the novel antioxidant, JP4-039, reduces the effects of acute radiation toxicity in the mouse retina.

This is a 2021 ARVO Annual Meeting abstract.