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Sachin Parikh, Steven Nusinowitz, Michael B Gorin, Anna Matynia; Retinal and visual pathway components mediating light- behavior in a mouse model of photoallodynia. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5261.
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© ARVO (1962-2015); The Authors (2016-present)
Specialized photoreceptors exist that either regulate biological states from defense, tropism and circadian photoentrainment or recognize images, movement and color. A painful response to light, photoallodynia is a shared symptom of disparate ocular conditions from cone-dominant dystrophies to corneal injury to migraine. These studies investigate the ocular contributions to light and pain perception using light aversion, a surrogate for photoallodynia.
We used a combination of genetic, surgical and pharmacological manipulations to dissect the relative contributions of photoreceptors, optic nerve and retinal pigment epithelium (RPE) to light aversion. Light aversion behavior at 1000 lux was quantitated as an aversion index (AI: ≤0=no aversion; 1=complete aversion) in wild type (WT) mice, mice lacking retinal and trigeminal melanopsin expressing cells (OPN4dta/dta) and mice lacking all known photoreceptors (OPN4dta/dta rd1), using optic nerve (ON) manipulations or enucleation. Nitroglycerin (NTG), a model for migraine, was used to unmask light aversion, and sodium iodate was used to chemically ablate the RPE.
Without NTG treatment, all mice with optic nerve lesions or enucleation exhibited no light aversion. NTG increased light aversion in WT mice with sham (AI=0.79±0.09, n=8), severe bilateral ON crush (AI=0.46±0.16, n=8), ON transection (AI=0.66±0.13, n=4), ON transection with RPE ablation (AI=0.62±0.19, n=4) or unilateral enucleation (AI=0.61±0.14, n=6). By contrast, light aversion did not increase after NTG in OPN4dta/dta mice with ON crush (AI=0.19±0.22, n=8), OPN4dta/dta rd1 double mutants (AI=0.12±0.02, n=4) or WT bilateral enucleation (AI=0.01±0.04, n=6).
In disease- and injury-free conditions, the retina and optic nerve are the predominant mediators of light aversion. By contrast, multiple pathways for light aversion are recruited in pathological states that exist beyond the optic nerve and retina although associated trigeminal nerves or other structures in the globe are required. NTG provides a useful tool for identifying the neural circuit(s) underlying this latent light perception. Melanopsin expression has been observed in a subset of trigeminal ganglion neurons that respond to light ex vivo, providing a potential alternative circuit to influence light aversion.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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