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Topical mydriatics affect light-evoked retinal responses in anesthetized mice.

ABSTRACT: To characterize effects of the muscarinic antagonist atropine (A) and the alpha-adrenergic agonist, phenylephrine (P), on mydriasis and light-evoked signaling in mice anesthetized by ketamine and xylazine (K+X).Pupillary areas of anesthetized C57BL/6 mice were measured, with or without topical application of A or A+P. Dark-adapted ERGs were recorded from 2- to 4-month-old C57BL/6 and 7.5-month-old albino hrhoG/hrhoG mice after application of A or P singly or in combination, before or after induction of K+X anesthesia. Effects of GABA were tested in the hrhoG/hrhoG mice.K+X anesthesia resulted in maximum mydriasis that was not enhanced by A or A+P. Dark-adapted b-wave amplitudes (-1.3 log sc td s) after K+X anesthesia were similar with or without A or P. A+P in the presence of K+X produced a slow growth in b-wave amplitude, reaching a plateau of twofold enhancement in 1 hour. Recordings of responses to varying flash energies revealed that the effects of A+P were on the maximum amplitude of the a- and b-waves and not on their sensitivity. Scotopic threshold responses were augmented as well. In photoreceptor-degenerated mice (hrhoG/hrhoG), an electronegative ERG wave recorded with K+X+A, was converted to a gamma-aminobutyric acid (GABA)-sensitive response with two electropositive components with A+P after K+X.Topical administration of A and P together, but not separately, in the presence of K+X, leads to a slow, dramatic enhancement of a- and b-waves by an unknown mechanism independent of pupil dilation.

SUBMITTER: Mojumder DK

PROVIDER: S-EPMC2869068 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Topical mydriatics affect light-evoked retinal responses in anesthetized mice.

Mojumder Deb Kumar DK Wensel Theodore G TG

Investigative ophthalmology & visual science 20090806 1

<h4>Purpose</h4>To characterize effects of the muscarinic antagonist atropine (A) and the alpha-adrenergic agonist, phenylephrine (P), on mydriasis and light-evoked signaling in mice anesthetized by ketamine and xylazine (K+X).<h4>Methods</h4>Pupillary areas of anesthetized C57BL/6 mice were measured, with or without topical application of A or A+P. Dark-adapted ERGs were recorded from 2- to 4-month-old C57BL/6 and 7.5-month-old albino hrhoG/hrhoG mice after application of A or P singly or in co ...[more]

PMID: 19661232

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Project description:A small number (<2%) of mammalian retinal ganglion cells express the photopigment melanopsin and are intrinsically photosensitive (ipRGCs). Light depolarizes ipRGCs and increases intracellular calcium levels ([Ca2+]i) but the signaling cascades underlying these responses have yet to be elucidated. To facilitate physiological studies on these rare photoreceptors, highly enriched ipRGC cultures from neonatal rats were generated using anti-melanopsin-mediated plate adhesion (immunopanning). This novel approach enabled experiments on isolated ipRGCs, eliminating the potential confounding influence of rod/cone-driven input. Light induced a rise in [Ca2+]i (monitored using fura-2 imaging) in the immunopanned ipRGCs and the source of this Ca2+ signal was investigated. The Ca2+ responses were inhibited by 2-aminoethoxydiphenyl borate, SKF-96365 (1-2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl-1H-imidazole), flufenamic acid, lanthanum, and gadolinium, consistent with the involvement of canonical transient receptor potential (TRP) channels in ipRGC phototransduction. However, the contribution of direct Ca2+ flux through a putative TRP channel to ipRGC [Ca2+]i was relatively small, as most (approximately 90%) of the light-induced Ca2+ responses could be blocked by preventing action potential firing with tetrodotoxin. The L-type voltage-gated Ca2+ channel (VGCC) blockers verapamil and (+)-cis-diltiazem significantly reduced the light-evoked Ca2+ responses, while the internal Ca2+ stores depleting agent thapsigargin had negligible effect. These results indicate that Ca2+ influx through VGCCs, activated after action potential firing, was the primary source for light-evoked elevations in ipRGC [Ca2+]i. Furthermore, concurrent Ca2+ imaging and cell-attached electrophysiological recordings demonstrated that the Ca2+ responses were highly correlated to spike frequency, thereby establishing a direct link between action potential firing and somatic [Ca2+]i in light-stimulated ipRGCs.

Project description:BackgroundPre-clinical testing of retinal pathology and treatment efficacy depends on reliable and valid measures of retinal function. The electroretinogram (ERG) and tests of visual acuity are the ideal standard, but can be unmeasurable while useful vision remains. Non-image-forming responses to light such as the pupillary light reflex (PLR) are attractive surrogates. However, it is not clear how accurately such responses reflect changes in visual capability in specific disease models. The purpose of this study was to test whether measures of non-visual responses to light correlate with previously determined visual function in two photoreceptor degenerations.MethodsThe sensitivity of masking behavior (light induced changes in running wheel activity) and the PLR were measured in 3-month-old wild-type mice (WT) with intact inner retinal circuitry, Pde6b-rd1/rd1 mice (rd1) with early and rapid loss of rods and cones, and Prph2-Rd2/Rd2 mice (Rd2) with a slower progressive loss of rods and cones.ResultsIn rd1 mice, negative masking had increased sensitivity, positive masking was absent, and the sensitivity of the PLR was severely reduced. In Rd2 mice, positive masking identified useful vision at higher light levels, but there was a limited decrease in the irradiance sensitivity of negative masking and the PLR, and the amplitude of change for both underestimated the reduction in irradiance sensitivity of image-forming vision.ConclusionsTogether these data show that in a given disease, two responses to light can be affected in opposite ways, and that for a given response to light, the change in the response does not accurately represent the degree of pathology. However, the extent of the deficit in the PLR means that even a limited rescue of rod/cone function might be measured by increased PLR amplitude. In addition, positive masking has the potential to measure effective treatment in both models by restoring responses or shifting thresholds to lower irradiances.

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Topical mydriatics affect light-evoked retinal responses in anesthetized mice.

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Topical mydriatics affect light-evoked retinal responses in anesthetized mice.

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