Abstract
Purpose :
IRBP plays a vital role in the visual cycle. Our group previously reported retinal degeneration (RD) and profound myopia in IRBP knockout (KO) on the C57BL6J background. The purpose of this study was to test whether IRBP KO on a DBA2 background would exhibit the same myopia as we observed on the C57BL6J background.
Methods :
Both male and female and littermate controls were used. The genotype of mice was masked during the experiments. At P140-150, IRBP heterozygous (N=3) and IRBP KO (N=3) mice on the DBA2 background (N5F1) were subjected to whole-eye ocular biometry/SD-OCT, fundoscopy, ERG, body weight and body length examinations. Data are reported as mean ± SEM. Using an unpaired t-test with Welch's correction, a p-value < 0.05 was considered significant.
Results :
We observed that myopia driven by IRBP deficiency overrides background differences. Data analysis revealed a significant increase in the total axial length (TAL) in IRBP KO compared with IRBP+/- mice (3899 ± 44.24 mm in KO, 3675 ± 35.74 in IRBP+/-, p=0.018). The primary contributor to increased TAL was vitreous chamber depth (VCD) in the KO (VCD, 979 ± 59.28 mm in KO, 569 ± 35.74 in IRBP+/-, p=0.0128). Myopia was accompanied by a 30% decline in total retinal thickness (RT) in KO (148.5 ± 2.57 mm in KO, 213.3 ± 1.202 in IRBP+/-, p=0.0002). A significant 40% decline in the amplitudes of a- and b- waves under both scotopic and photopic conditions was observed in IRBP KO compared with IRBP+/-. No significant differences were observed in central corneal thickness, anterior chamber depth, and lens thickness. Body weight (30.9 ± 3.51 grams in KO, 33.9 ± 2.46 in IRBP+/-) and length (4.367 ± 0.185 cm in KO, 4.433 ± 0.2186 in IRBP+/-) remained unaltered.
At a similar age, IRBP KO on the C57BL6J background, showed similar phenotype with TAL, 3696 ± 22.37 mm , 3445 ± 9.957 in C57 WT, p=0.0004 ; VCD, 766 ± 25.75 mm in KO, 548 ± 50.57 in C57 WT, p=0.0150; and RT, 207 ± 8.35 mm in KO, 166 ± 5.833 in C57 WT, p=0.0104.
Conclusions :
Our data support the hypothesis of a similar ocular phenotype of IRBP KO on both inbred DBA2 and C57BL6J backgrounds. This indicates that the role of IRBP in myopia and RD is independent of strains/background. This also suggests similar mechanisms are associated with IRBP function in determining the axial length and prevention of photoreceptor death.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.