Abstract
Purpose :
Age-related Macular Degeneration (AMD) is a leading cause of blindness with the number of affected individuals only predicted to increase in the coming decades due to the aging population of developed nations. There exists very few models of AMD which accurately replicate disease pathology to better understand disease mechanisms. One model, injection of sodium iodate, results in a rapid and severe onset of RPE death followed closely by photoreceptor degeneration. Here we present data on developing a new model using multiple, low-dose injections of sodium iodate in an attempt to damage the RPE and cause a slow photoreceptor degeneration similar to that seen in human AMD patients.
Methods :
Adult Brown-Norway rats were used. Sodium Iodate was diluted to between 5mg/mL and 40mg/mL and injected via the intraperitoneal route once or every other day from either a single day or up to 14 days. Prior to the initial administration animals were assessed using OCT and fundus photography to establish baseline measurements. Animals were then assessed weekly out to 4 weeks post injection and then again 4 weeks later before their eyes were enucleated and embedded for histology or for RPE flatmount to assess neural retina and RPE health. The thickness of the outer nuclear layer and OSEL was measured.
Results :
The initial phase using 5mg/kg daily for 14 days, 7.5mg/kg daily for 7 days, and 12.5mg/kg every other day for 8 days showed no overt phenotypic changes out to 4 weeks post injection. OCT measurements of ONL thickness (5mg/kg: 50.1µm vs 49.4µm, p=0.26; 7.5mg/kg: 49.1µm vs 49.2µm, p=0.97 ; 12.5mg/kg: 50.0µm vs 49.6µm, p=0.81) and OSEL thickness (5mg/kg: 23.5µm vs 24.4µm, p=0.12; 7.5mg/kg: 23.9µm vs 24.3µm, p=0.51; 12.5mg/kg: 23.7µm vs 25.1µm, p=0.01 ) were not statistically different from baseline except for OSEL in the 12.5mg/kg group with significantly thicker OSEL layer.
Conclusions :
Our initial attempts were unable to produce any photoreceptor degeneration within 4 weeks as measured by OCT. Further analysis of these animals at the histological level are ongoing to determine if subtle cellular defects are detectable with repetitive, low dose sodium iodate treatment. Additionally, higher doses closer to the proposed minimum effective dose (15-20mg/kg, once), which may be more effective, will be tested. Our goal is to identify indicators of RPE health to determine if low dose sodium iodate is capable of damaging RPE.
This is a 2020 ARVO Annual Meeting abstract.