Suppression of Drusen-like Deposits by a Novel VCP modulator in CCR2 Deficient Mice

Abstract

Purpose: VCP is a ubiquitously expressed ATPase that is reported to be involved in several physiological activities as well as neurodegeneration. In this study, we investigated whether our newly developed novel VCP modulator could resolve drusen-like deposits in eyes of older CCR2 deficient mice (experiment 1) or suppress deposit formation in eyes of younger CCR2 deficient mice (experiment 2).

Methods: The mice were orally administered either a VCP modulator (Kyoto University Substance [KUS] group; n = 15) or saline (control group; n = 24) from the ages of 9 months and 2 months in experiments 1 and 2, respectively. Fundus photographs were used to determine the number of drusen-like deposits at each evaluation point.

Results: Experiment 1: The number of deposits in the KUS group at 6 months of age (baseline) was similar to that observed in the control group (7.5 ± 9.8 and 10.3 ± 10.9, respectively). Although the deposits in the control group increased with age, those in the KUS group did not (100.7 ± 99.3 and 12.3 ± 22.1, respectively, at 15 months) and were significantly less in number than those in the control group from 11-15 months of age (P < 0.01). During observation, the number of deposits appeared to have decreased in the eyes of some mice in the KUS group. Experiment 2: The number of deposits in the control group was not significantly different from those in the KUS group at 2 months of age (baseline). The number of deposits in the control group increased with age, while those in the KUS group did not. At 9 months of age, the number of deposits in the KUS group was significantly lesser than those in the control group (4.4 ± 3.5 vs. 22.8 ± 28.5, respectively, P < 0.01).

Conclusions: KUS, a novel modulator, can be used to suppress the formation of drusen-like deposits in the eyes of CCR2 deficient mice.

Keywords: 504 drusen • 412 age-related macular degeneration