Abstract
Purpose :
Previous research demonstrated the therapeutic efficacy of peroxisome proliferator-activated receptors α (PPARα) agonists on retinal diseases. Fenofibrate, a PPARα agonist, has been formulated into microparticles (Feno-MP, Granted Patent # US 11369575B2) to achieve controlled and sustained release. This study aimed to evaluate the therapeutic potential of Feno-MP in an age-related macular degeneration (AMD) murine model.
Methods :
One µL aqueous suspension of Feno-MP or Blank-MP (125 µg) with/without Fenofibrate (30 µg) was intravitreally injected into very low-density lipoprotein receptor gene knockout (Vldlr-/-) mice at 2 months of age. Retinal function was evaluated using Electroretinography (ERG). At six months post-injection, peanut agglutinin (PNA) lectin staining of cone photoreceptors was conducted on flat-mounted retinas. Retinal and subretinal neovascular lesions were assessed through fundus fluorescein angiography and Isolectin-IB4 staining.
Results :
The photopic a-wave amplitudes in the Feno-MP group were higher than those of the Blank-MP group at one, three, and five months post-injection in Vldlr-/- mice, suggesting that Feno-MP prevented cone functional decline (n = 5, p < 0.01). In addition, Feno-MP alleviated the decreased density of cone photoreceptors with PNA staining in both central and peripheral retinas (n = 5, p < 0.05). Feno-MP significantly decreased the number of retinal vascular leakage spots and leakage spot area relative to Blank-MP (n = 4, p < 0.05). As shown by Isolectin-IB4-staining, the number of subretinal neovascularization (SRNV) was declined from 15.2 (±0.41) per eye in the Blank-MP group to 10.1 (±1.47) in the Feno-MP group (p < 0.01), and intraretinal neovascularization (IRNV) was decreased from 25.6 (±2.29) per eye in the Blank-MP group to 15.2 (±1.24) per eye in the Feno-MP group (p < 0.01). Additionally, the areas of SRNV and IRNV lesions were decreased in Feno-MP treated Vldlr-/- mice relative to the Blank-MP Vldlr-/- mice (n = 5, p < 0.05).
Conclusions :
Intravitreal Feno-MP injection ameliorated retinal photoreceptor loss, vascular leakage and subretinal neovascularization in Vldlr-/- mice, suggesting therapeutic potential for wet AMD.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.