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Hilde Rogeberg Pedersen, Maureen Neitz, Stuart J. Gilson, Erlend Sommer Landsend, Øygunn Aas Utheim, Tor Paaske Utheim, Rigmor C Baraas; PAX6 genotype and thickness of retinal layers in aniridia. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1896. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the relationship between genotype and thickness of retinal layers in congenital aniridia.
The study included 36 participants (14 males) with congenital aniridia (10–72yrs) and 32 age-matched normal controls (12 males). DNA, isolated from saliva samples from 34 participants, was used in the PCR to amplify and sequence the exons and intron/exon junctions of the PAX6 gene, with previously described primers and conditions. Fluorescent DNA sequencing was performed on both DNA strands. Ocular biometry was measured with Zeiss IOLMaster 700. SD-OCT images were acquired with the Heidelberg Spectralis OCT2. Horizontal B-scans were segmented semi-automatically and mean thicknesses were calculated of inner (IRL: including RNFL, GCL and IPL) and outer retinal layers (ORL: including ONL, photoreceptor IS and OS, RPE) within 5 regions: Fovea (central 50µm), inner region 0.5–1.5mm and outer region 1.5–3.0mm retinal eccentricity along nasal and temporal meridians.
PAX6 mutations were found in 26 (76.5%) of those with aniridia, with 16 having mutations predicted to cause haploinsufficiency. Two had mutations predicted to cause a protein C-terminal extension (CTE) and eight had PAX6 mutations with uncertain effect on protein. Non-coding regions of the PAX6 gene (5′UTR: exons 1–4) were involved in four mutation variants. Foveal hypoplasia was observed in 92.3% of those with aniridia. Aniridic eyes were on average significantly shorter (p<0.001) and foveal IRL were thicker at the expected foveal center (p<0.001), but thinner in other regions (p<0.01) compared to normal controls. ORL were significantly thinner across the horizontal meridian compared to normal controls (p<0.001), particularly in the fovea (mean±SD 156.3±32.3 µm vs 212.1±13.7 µm, p<0.001). No correlations were observed between axial length and foveal ORL or IRL. Within each mutation type there was large variability in retinal phenotype, however, persons with mutations in the 5′UTR had, on average, thicker foveal ORL than those with mutations in the coding region (exons 5–13; p=0.002). The two individuals with CTE mutations had the greatest reduction in foveal ORL and the shortest AL.
PAX6 mutations are associated with significant thinning of inner and outer retinal layers, consistent with misdirected retinal development resulting in reduced number of neurons in the retina, with mutations in coding regions possibly giving the worst outcome.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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