Protection of Retinal Cells against Proliferative Vitreoretinopathy after Ocular Trauma

Abstract

Purpose : After ocular trauma, preservation of vision is challenging, particularly with cases resulting in retinal detachment (RD). Reattachment failure is a prevalent risk due to improper wound healing leading to proliferative vitreoretinopathy (PVR). Hemorrhage into the vitreoretinal space is a risk factor for PVR, and reactive oxygen species (ROS) generated by cellular interaction with blood-derived cytotoxic components enhance oxidative stress, damaging retinal cell function and contributing to its development. In this study, the effectiveness of a new protein therapeutic for scavenging cytotoxic blood components and its sustained delivery by polydopamine nanoparticles (PDA NPs) was investigated as a novel strategy to protect against PVR development after RD.

Methods : Primary porcine Müller glial cells were used to investigate the benefit of a novel blood-sourced protein therapeutic. Incorporation of therapeutic (t) into a sustained delivery system was achieved by surface loading PDA NPs (tPDA NPs). Cytotoxicity of the therapeutics was measured with MTS. Intracellular ROS and α-SMA expression after co-treatment of therapeutic and H₂O₂ or ferric ammonium citrate (FAC) challenge was measured by immunofluorescence.

Results : The investigated protein therapeutic showed no significant cytotoxicity to primary retinal cells up to 10 mg/mL concentration. tPDA NPs had no measurable cytotoxicity at 50 µg/mL and below. Co-treatment with protein therapeutic or tPDA NPs significantly reduced oxidative stress induced by 200 μM H₂O₂ and 10 μg/mL FAC challenge. Oxidative stress reduction, after H₂O₂ or FAC challlenge, in Muller glial cells were 40 ± 11% and 56 ± 15 % (p ≤ 0.05) at 2 mg/mL of protein therapeutic. tPDA NPs reduction of 53 ± 3% (p ≤ 0.05) at 50 µg/mL after H₂O₂ treatment. Protein therapeutic reduced α-SMA expression after oxidative challenge.

Conclusions : This work focused on studying a scavenging protein therapeutic and its sustained delivery for protection of retinal cells. The therapeutic showed no toxicity to primary porcine Müller glial cells and reduced oxidative stress after oxidative challenge. Altogether, application of a protective scavenging protein therapeutic by sustained release redox-responsive PDA NPs shows potential to reduce factors associated with PVR.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Oxidative stress reduction by protein therapeutic and tPDA NPs after H₂O₂ or FAC challenge (p≤ 0.05, *) and α-SMA expression was also reduced.