Abstract
Purpose :
The presence of geographic atrophy (GA) is an essential factor for the diagnosis of non-neovascular age-related macular degeneration (AMD). The lack of an animal model that shows GA prograssion has hampered reserch and development of new treatments. The current study developed a macaque model of GA indiced by intravitreal injection of sodium iodate (SI).
Methods :
Thirty minutes prior to intrviteral SI injection into the right eye (0.2-0.4 mg/kg) macaques received either vehicle or the antioxidant edaravone (3 mg/kg/hr, i.v.) and were treated for a total of 2 hours. Fundus photography and optical coherence tomography (OCT) were performed before and 1, 2, 4, 6, 8, 12, and 16 weeks following SI injection. Statistical analysis was performed using two-way repeated measures ANOVA followed by t-test. P < 0.05 was considered significant.
Results :
Fundus auto-fluorescence (FAF) revealed GA-like demarcated areas after SI injection. The area of GA (pix2) rapidly increase during the first 2 weeks and then gradually increased over time--at 16 weeks after SI injection, the area (mean±SEM) was 99625±7646. Edaravone significantly inhibited GA progression: at 16 weeks, GA area was 40323±17556.
OCT imaging of SI-injected eyes revealed atrophy of photoreceptors and RPE, especially in the central fovea area. In additon, drusen-like deposits develop below the RPE. OCT imaging also demonstrated retinal and outer nuclear layer (ONL) thinning. During the first 2 weeks following SI treatment, rapid thinning of the retina was observed followed by a gradual decrease of thinning for the rest of the study period. Retinal thickness before and 16 weeks after SI injection was 303.7±7.7 µm and 158.1±14.3 µm, respectively. Edaravone tended to inhibit retinal thinning.
Fluorescein angiography (FA) revealed that SI-injected eyes showed a window defect in the central fovea area in 4 out of a total of 6 eyes. In the edaravone group, only one animal showed a window defect.
Histological examination confirmed degeneration of the structures in the fovea centralis region of the SI-injected eye.
Conclusions :
Intrviterally-injection of SI led to a reproducible model of nonexudative AMD with GA that mimics many aspects of clinical AMD. Aantioxidant treatment could delay progression of GA. The current macaque model coud be useful for developing new therapeutic options for AMD with GA.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.