Fig. 4: DF-003 reduces microglial infiltration in the retinas of ROSAH model mice.

a Schematic of Alpk1^hALPK1 and Alpk1^hALPK1T237M alleles. Ex: exon; CDS: coding sequence. Generation of the two alleles was described in Methods. Mice homozygous for Alpk1^hALPK1 were designated as hALPK1-KI mice, while mice heterozygous for Alpk1^hALPK1 and Alpk1^hALPK1T237M, mimicking the genetic profile of ROSAH patients, were designated as hALPK1[T237M]-KI mice. b, c Female hALPK1-KI and hALPK1[T237M]-KI mice were treated orally with DF-003 once per day for 10 days at the indicated doses (n = 8 animals for each group). b At endpoint, anti-IBA1 antibody was used to label microglia on retinal cross-sections (green). c IBA1-positive cells in the outer nuclear layer (ONL) and inner nuclear layer (INL) of the retina from each mouse were quantified and normalized to the length of the curvature of the retina. Data represent means ± SEM of each genetic and treatment group, with each dot representing one section from one animal. Statistical comparisons between vehicle groups of the two genotypes were made using two-tailed unpaired Student’s t-tests: in INL, F = 5.740, t = 10.05, r² = 0.88, 95% confidence interval (CI) 1.21 to 1.86, df = 14, p = 0.000000088; in ONL, F = 3.759, t = 8.879, df = 14, r² = 0.85, 95% CI 4.11 to 6.72, p = 0.00000040; and comparisons between DF-003 dosed groups and vehicle group within the same genotype were made with one-way ANOVAs followed by Sidak’s post hoc tests: in the INL of hALPK1[T237M]-KI mouse retinas, t = 5.69, df = 21, 95% CI 0.59 to 1.48, p = 0.000024 between the vehicle and 3 mg/kg groups, and t = 4.87, df=21, 95% CI of 0.45 to 1.33, p = 0.00016 between the vehicle and 5 mg/kg groups; in the ONL of hALPK1[T237M]-KI mouse retinas, t = 4.28, df = 21, 95% CI 1.25 to 4.47, p = 0.00066 between the vehicle and 3 mg/kg groups, and t = 3.32, df = 21, 95% CI of 0.61 to 3.83, p = 0.0065 between the vehicle and 5 mg/kg groups.