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Kristie Ling Liao, Shanu Markand, Salma Ferdous, Kevin Joseph Donaldson, Jeffrey H Boatright, John M Nickerson; The effects of old age on RD and myopia in IRBP KO mice. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2335. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Interphotoreceptor retinoid-binding protein (IRBP, gene RBP3) is the most abundant protein in the subretinal space. Mutations in the human RPB3 gene are associated with high myopia and retinal dystrophy. The IRBP knockout (KO) mouse is a valuable tool to assess effects of IRBP deficiency. We previously reported both retinal degeneration (RD) and myopia phenotype in IRBP KO mice. The RD initiates at ~P23 and myopia begins at postnatal day 8 (P8). Previous studies focused at earlier time points. The current study examined RD and myopic changes in aged IRBP KO mice compared with aged C57BL/6J WT mice. We hypothesize that IRBP KO mice continue to exhibit myopia and RD phenotype at older (~2 years) ages.
Eye weights (mg), body weight (grams), and body length (inches) measurements were conducted in ~P700 WT (N=6) and IRBP KO mice (N=9). ERG was used to assess retinal function at ~P700 (N=8) and ~P500 (N=4) in IRBP KO mice. Retinal morphology was investigated at ~P700 (N=2). A two-way ANOVA with Tukey's multiple comparisons test and an unpaired t test with Welch's correction were used to assess statistical significance between groups. A p-value < 0.05 was considered significant.
IRBP KO mice had significantly heavier eyes (0.02948 ± 0.001 grams, p-<0.0001) than the WT mice (0.02648 ± 0.001 grams). ERG analysis demonstrated significant functional decline of both scotopic a- (p= 0.0002) and b-waves (p=0.0015) and photopic a- (p=0.0491) and b- (p=0.0018) waves in IRBP KO mice at ~P700. No significant differences were observed in the body weight (WT mice, 32.7± 5.94 grams, KO, 32.19 ± 4.47grams, p>0.9999) or body length (WT mice, 10.24 ± 1.641 cm, KO, 9.70 ± 0.558 cm, p>0.9999). The preliminary morphological assessment demonstrated thinner retinas and disrupted outer and inner segments.
Overall, our data supports the notion that aged IRBP KO mice continue to display myopic and RD changes. Future experiments will focus on quantification of retinal morphological alterations and investigating the underlying mechanisms of myopia in IRBP KO mice.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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