Abstract
Purpose: :
Polymorphic variations in the gene SERPING1, which codes for complement factor 1 inhibitor (C1INH), have been implicated in AMD development1. We plan to investigate the function of C1INH and its therapeutic potential in both an AMD mouse model, utilizing Ccl2/Cx3cr1-/-2,3 and wild type C57BL/6 mice.
Methods: :
Nine four week old C57BL/6 mice were selected for this initial study and divided into three groups. Each group received 25U/ml, 50U/ml or 100U/ml concentration of proprietary C1INH. The mice were anaesthetized with an intraperitoneal injection of 0.05ml of ketamine-xylazine (ketamine, 100 to 125 mg/kg of body weight; xylazine, 10 to 12.5 mg/kg) combination. The right eye of each mouse was dilated using Tropicamide 1%. A Hamilton syringe with a 33 gauge bevelled needle was used to deliver 1μl of C1INH into the subretinal space. A localised detachment was subsequently confirmed under the microscope. The treated and untreated retinas were photographed at 1 week post injection and the eyes fixed in Paraformaldehyde prior to processing.
Results: :
There was no gross difference, on direct visualisation, between the treated and untreated retinas in the 3 groups after 1 week. However, this was an initial toxicity study and histological examination may reveal significant changes during the time course of this experiment.
Conclusions: :
At this early stage no difference in retinal appearance has been noted between treated and untreated animals. On-going work, which will be presented at ARVO, including histological analysis may demonstrate differences in apoptosis levels or other ultrastructural changes. The results of this study will inform our future decisions for a larger body of work to examine the effect of SERPING1 in AMD in these murine models.
Keywords: age-related macular degeneration • proteins encoded by disease genes • retinal degenerations: cell biology