Direct and consensual murine pupillary reflex metrics: Establishing normative values

Hussain, Rehana Z.; Hopkins, Steven C.; Frohman, Elliot M.; Eagar, Todd N.; Cravens, Petra D.; Greenberg, Benjamin; Vernino, Steven; Stüve, Olaf

doi:10.1016/j.autneu.2009.07.021

Cited by 20 publications

(14 citation statements)

References 26 publications

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“…S5) and provided evidence of calcium homeostasis that is essential for photoreceptor maintenance. We used the pupil light response (PLR) (19), which has been validated in similar studies (3,(20)(21)(22), as a functional test that would prove not only the existence of light-sensing OS but also that efferent connections existed to central targets. We aimed to test for an improvement above the zero baseline in these mice that were structurally and functionally devoid of rods at the time of intervention and therefore measured the PLR before and after treatment to compare outcomes pairwise in the same animal.…”

Section: Resultsmentioning

confidence: 99%

“…We aimed to test for an improvement above the zero baseline in these mice that were structurally and functionally devoid of rods at the time of intervention and therefore measured the PLR before and after treatment to compare outcomes pairwise in the same animal. To avoid influences such as transplantation-related inflammation, we stimulated the transplanted eye and measured the consensual PLR (19) (Fig. 4A) in the unoperated eye after precursor cell transplantation (n = 12).…”

Section: Resultsmentioning

confidence: 99%

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Reversal of end-stage retinal degeneration and restoration of visual function by photoreceptor transplantation

Singh

Issa

Butler

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

224

211

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One strategy to restore vision in retinitis pigmentosa and agerelated macular degeneration is cell replacement. Typically, patients lose vision when the outer retinal photoreceptor layer is lost, and so the therapeutic goal would be to restore vision at this stage of disease. It is not currently known if a degenerate retina lacking the outer nuclear layer of photoreceptor cells would allow the survival, maturation, and reconnection of replacement photoreceptors, as prior studies used hosts with a preexisting outer nuclear layer at the time of treatment. Here, using a murine model of severe human retinitis pigmentosa at a stage when no host rod cells remain, we show that transplanted rod precursors can reform an anatomically distinct and appropriately polarized outer nuclear layer. A trilaminar organization was returned to rd1 hosts that had only two retinal layers before treatment. The newly introduced precursors were able to resume their developmental program in the degenerate host niche to become mature rods with light-sensitive outer segments, reconnecting with host neurons downstream. Visual function, assayed in the same animals before and after transplantation, was restored in animals with zero rod function at baseline. These observations suggest that a cell therapy approach may reconstitute a light-sensitive cell layer de novo and hence repair a structurally damaged visual circuit. Rather than placing discrete photoreceptors among preexisting host outer retinal cells, total photoreceptor layer reconstruction may provide a clinically relevant model to investigate cell-based strategies for retinal repair.stem cell | blindness | retinal surgery | visual cortex | neural regeneration

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Reversal of end-stage retinal degeneration and restoration of visual function by photoreceptor transplantation

Singh

Issa

Butler

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

224

211

View full text Add to dashboard Cite

show abstract

“…Pupillary responses have been used as important measures of optic nerve function in optic neuritis and MS patients (Ellis, 1979; Beck et al, 1992; Surakka et al, 2008). Pupillometry has been used recently to characterize normal murine pupillary light responses and the role of melanopsin-containing RGCs (Zhu et al, 2007; Hussain et al, 2009). A potential role for pupillometry in monitoring optic nerve function in EAE mice was suggested (Hussain et al, 2009), but has not been reported.…”

Section: Introductionmentioning

confidence: 99%

“…Pupillometry has been used recently to characterize normal murine pupillary light responses and the role of melanopsin-containing RGCs (Zhu et al, 2007; Hussain et al, 2009). A potential role for pupillometry in monitoring optic nerve function in EAE mice was suggested (Hussain et al, 2009), but has not been reported.…”

Section: Introductionmentioning

confidence: 99%

In vivo detection of experimental optic neuritis by pupillometry

Shindler

Revere

Dutt

et al. 2012

Experimental Eye Research

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Optic neuritis is an inflammatory demyelination of optic nerve often occurring in multiple sclerosis (MS) patients. Mice with experimental autoimmune encephalomyelitis (EAE), an MS model, develop optic neuritis, but it is detected histologically after sacrifice, limiting the ability to monitor progression or treatment in vivo. We examined whether pupillary light responses measured by pupillometry can identify eyes with optic neuritis in EAE mice. C57BL/6 mice were exposed to unilateral light flashes of increasing intensity at 10 second intervals (4.7, 37, and 300 μW/cm2). Pupillary responses were recorded with a commercially available pupillometer. EAE was then induced by immunization with myelin oligodendrocyte glycoprotein. Pupillometry was repeated up to 17 days post-immunization, and responses were correlated with optic nerve inflammation. By day 17 post-immunization, 90% of EAE eyes had optic nerve inflammation. EAE eyes had significantly reduced pupillary constriction compared to control eyes. Mice exhibited more than a 25% decrease in pupillary constriction in at least one eye by days 13-15 post-immunization. In some eyes, pupil responses decreased prior to onset of detectable inflammation. Results show that pupillometry detects decreased optic nerve function in experimental optic neuritis, even in the absence of histological detection. Measuring pupillary constriction allows in vivo identification and functional assessment of eyes with optic neuritis that will be useful in evaluating potential therapies over time. Furthermore, results demonstrate that decreased visual function occurs early in optic neuritis, before optic nerve inflammation reaches its peak level.

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“…2) to measure the murine pupillary light reflex (Mure et al, 2007;Hussain et al, 2009). Recently similar LED-based chromatic pupillometry was employed by Herbst et al (2011) to study the human pupillary light reflex (PLR).…”

Section: Mouse Pupillometrymentioning

confidence: 99%