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TS Aleman, ML Scott, RJ Chen, JD Chico, AY Cheung, JP Van Hooser, TM Redmond, K Palczewski, SG Jacobson, AV Cideciyan; Impairment of the Pupillary Light Reflex in Rpe65-/- Mice and Patients with Leber Congenital Amaurosis . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3490.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To characterize the pupillary light reflex (PLR) in a murine model of Leber congenital amaurosis (LCA) and patients with the disease. Methods: Direct PLR was recorded using a custom-built pupillometer in anesthetized, dark-adapted Rpe65-/- and control mice, 8-12 weeks of age. PLRs were elicited with increasing intensities (∼8 log u range) of 100 ms duration full field light stimuli. Oral 9-cis-retinal was administered to a subset of Rpe65-/- mice. PLR was recorded before and 1 week after cis-retinoid treatment. A group of patients with uncomplicated LCA underwent dark-adapted pupillometry using a comparable system Results: Baseline pupillary diameters in Rpe65-/- and control mice were similar. PLR thresholds of Rpe65-/- mice were elevated by 3-4 log u compared to those of controls. The waveforms of the PLR in Rpe65-/- mice could be simulated with ∼4 log dimmer stimuli presented to control mice. Supplementation with 9-cis-retinal lowered the PLR threshold by ∼2 log. LCA patients had baseline pupillary diameters similar to normal, but the PLR was abnormal with thresholds elevated by 3-5 log u. Pupillary constriction to brighter stimuli had smaller amplitude and slower kinetics than normal. Conclusions: Pupillometry was used to quantify the visual impairment and to probe transmission of retinal signals to higher nervous centers in a murine model of LCA and in LCA patients. The objective and non-invasive nature of the PLR measurement and the observed post-treatment change toward normal in the animal model suggest that this may be a useful additional outcome measure in future therapeutic trials of LCA.
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