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M. C. Canver, K. E. Revere, G.-S. Ying, A. C. Canver, J. Bennett, D. C. Chung; Impairment of Pupillary Light Responses in Murine Models of Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4048.
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© ARVO (1962-2015); The Authors (2016-present)
To establish normative reference values for pupillary light response (PLR) parameters during disease progression in comparison with those of selected murine models of retinal degeneration.
Cohorts of wildtype (C57Bl6) and retinal degeneration (nrl-/-, rd10-/-) mice underwent PLR testing, utilizing the Neuroptics Pupillometer (San Clemente, CA, USA). Mice were tested at postnatal day 21 (P21), 35(P35), 49(P49) and if indicated 77(P77). Mice were dark-adapted for >12 hours prior to testing and exposed to three light pulses at 10 second intervals at three intensities: 4.6, 37.5, 300 µW/cm2, with left and right eyes exposed in alternating fashion. Both direct and consensual responses were measured. A custom algorithm for automated analysis of the raw pupillometric data was formulated and facilitated the extraction of twelve physiologically relevant parameters: (1) baseline diameter, (2) minimum amplitude, (3) response amplitude, (4) re-dilation amplitude, (5) percent constriction, (6) response time, (7) re-dilation time, (8) average constriction velocity, (9) average re-dilation velocity, (10) maximum constriction velocity, (11) maximum re-dilation velocity, and (12) onset latency. Normative parameters for each mouse strain were established as a function of age for all 12 parameters. Within each mouse strain, each of the 12 parameters was compared for each intensity using the GENMOD procedure to analyze changes over time.
C57Bl6 wildtype strain had robust PLR responses at all light intensities and the PLRs did not exhibit significant changes over the test period. In contrast, rd10-/- mice exhibited significant impairment of PLRs between 3 and 7 weeks. PLRs also diminished in the nrl-/- mice over time, especially at lower light intensities. The timecourse of PLR changes in the retinal degeneration mice correlated with changes in the outer nuclear cell layer (ONL) thickness over time.
Pupillometric measures are non-invasive, rapid, and quantitative and can be used as outcome measures in assessments of treatment efficacy of pharmacologic and gene based therapies in mice.
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