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Helena email@example.com Lee, Jennifer Scott, Helen Griffiths, Andrew J Lotery; Murine Retinal Development, Morphology and Function in Albinism: Potential Implications for Therapeutic Development. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5570.
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© ARVO (1962-2015); The Authors (2016-present)
Albinism is a disorder of melanin biosynthesis characterised by abnormal retinal development & visual impairment, for which there is a paucity of effective treatments. Preclinical studies in murine albinism models are essential to develop novel therapeutics. It is necessary to develop a detailed understanding of in-vivo retinal development, morphology & function prior to performing proof of concept treatment studies. In this study, we characterise the retinal phenotype of the C57BL/6J-c2J null mouse model of oculocutaneous albinism (OCA).
We obtained 53 mixed cross-sectional and longitudinal in-vivo optical coherence tomography (OCT) and electroretinography (ERG) examinations from 9 C57BL/6J-c2J OCA mice at 4, 5, 6, 8, 12 & 16 weeks of age, which were compared to 110 examinations from 11 C57Bl/6J control mice. Retinal layer segmentation was performed using Bioptigen InVivoVue Diver 2.4 software. Generalised linear mixed regression modelling was used to analyse group differences.
In comparison to control mice, there was evidence of a significant reduction in the combined ganglion cell & inner plexiform layer (p<0.01) and retinal pigment epithelium (p<0.0001) thickness measurements in OCA mice. Interestingly, the photoreceptor inner segment (IS) appeared to be significantly thicker in OCA (p<0.0001). We observed a decrease in photoreceptor IS, outer segment (OS) and end-tips (ETPRS) thickness between four and six weeks of age, followed by an increase in both groups. The magnitude of increase was greater in control mice, resulting in a significantly greater OS thickness at eight (p<0.01), twelve (p<0.0001) & sixteen (p<0.0001) weeks of age, ETPRS thickness at twelve (p<0.01) & sixteen (p<0.01) weeks of age, and elimination of the group differences in IS thickness by sixteen weeks. This corresponded with significant reductions in A (p<0.05) & B-wave (p<0.01) wave amplitudes on ERG in OCA, with mean (SD) A & B-wave amplitudes of -98.3 (62.9) µV & 219.1 (90.1) µV in OCA and -113.0 (66.5) µV & 261.8 (98.9) µV in control mice, respectively.
We have characterised the retinal phenotype of the C57BL/6J-c2J null mouse model of OCA, and identified several OCT biomarkers, which could be used to monitor in vivo murine responses to potential drug treatment(s). This is important for future translational studies & therapeutic development in albinism.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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