Intravitreal HC-HA/PTX3, a soluble matrix component of amniotic membrane, inhibits proliferative vitreoretinopathy (PVR) in a mouse model of PVR

Abstract

Purpose : Proliferative vitreoretinopathy (PVR) occurs in 10% of retinal detachments and is the most common cause of failure of retinal detachment surgery. There are currently no approved treatments for inhibiting PVR. We studied the ability of intravitreal HC-HA/PTX3, a soluble matrix component of amniotic membrane, to inhibit PVR in a mouse model. Additionally, we assessed the safety of intravitreal HC-HA/PTX3 on the mouse retina.

Methods : PVR was induced in 38 control and 43 treatment eyes of 6-8 week old female C57BL/6J mice. A posterior vitreous detachment was induced by intravitreal injection of 0.5μL SF₆ gas. One week later, immediately prior to injection, freshly harvested ARPE-19 cells (immortalized retinal pigment epithelial cells [RPE]) were mixed with PBS alone (control) or PBS with HC-HA/PTX3 to yield solutions containing 2x10⁴ RPE cells and 0.15 (n=15), 0.30 (n=15), or 0.6 (n=13) μg/ml HC-HA/PTX3 per microliter. 1μL of the solution was injected intravitreally and weekly fundus photos were used to grade PVR development for 4 weeks. Additionally, mice received intravitreal injection of PBS (n=2) or 0.6 μg/ml HC-HA/PTX3 (n=5) and ERG a- and b-wave amplitudes compared after 4 weeks to assess safety. Mann-Whitney U test was used to compare PVR grades.

Results : After 4 weeks, eyes injected with RPE/PBS (control mice) developed a mean PVR grade of 2.75 out of 6 (SD: 1.35), which was significantly higher than mice treated with intravitreal 0.6 μg/ml HC-HA/PTX3 (1.77, SD: 0.73, p = 0.018). The difference in PVR grade compared to control mice approached statistical significance in mice treated with intravitreal 0.3 μg/ml HC-HA/PTX3 (1.93, SD: 1.16, p = 0.062) and was not significantly different compared to mice treated with intravitreal 0.15 μg/ml HC-HA/PTX3 (2.93, SD: 1.44, p = 0.803). There was no difference in a or b wave ERG amplitudes after 4 weeks in mice treated with intravitreal PBS or 0.6 μg/ml HC-HA/PTX3.

Conclusions : Intravitreal HC-HA/PTX3 (0.6 μg/ml) inhibits PVR in a pre-clinical mouse model without any deleterious effects on ERG amplitude measurement.

This is a 2021 ARVO Annual Meeting abstract.