Light aversion and corneal mechanical sensitivity are altered by intrinscally photosensitive retinal ganglion cells in a mouse model of corneal surface damage

Matynia, Anna; Parikh, Sachin; Deot, Neal; Wong, Arie; Kim, Paul; Nusinowitz, Steven; Gorin, Michael B.

doi:10.1016/j.exer.2015.05.025

Cited by 28 publications

(26 citation statements)

References 46 publications

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“…We analyzed tissue extracts from regions with peripherally and centrally targeted trigeminal axon projections, as well as the ganglia for melanopsin mRNA (Le Pichon and Chesler, 2014 ). Cornea, iris, choroid, brainstem (encompassing the trigeminal nuclei), and TG express melanopsin mRNA, but not lens, cerebellum or the same tissues from mice that express diphtheria toxin under control of the melanopsin promoter (OPN4 dta/dta ) (Matynia et al, 2012 , 2015 , Figure 1E ). Melanopsin is deleted in this strain and the cells normally expressing melanopsin are ablated.…”

Section: Resultsmentioning

confidence: 99%

“…The light-aversion assay was performed as previously described with modifications (Matynia et al, 2012 , 2015 ). Briefly, a two-chamber box with an open, light, and closed, dark section was used to measure time spent in the light compartment.…”

Section: Methodsmentioning

confidence: 99%

“…Melanopsin has also been identified in rare cell bodies in the iris, in projections to the ciliary body and as a modulator of vascular development and dilation (Xue et al, 2011 ; Rao et al, 2013 ; Semo et al, 2014 ; Sikka et al, 2014 ). In mice, ipRGCs mediate innate and corneal surface damage-induced light aversion (Johnson et al, 2010 ; Semo et al, 2010 ; Thompson et al, 2010 ; Matynia et al, 2012 , 2015 ) and in patients, are important for migraine-associated photoallodynia (Noseda et al, 2010 ). Although pain can be felt in various ocular tissues, the retina itself does not sense pain.…”

Section: Introductionmentioning

confidence: 99%

“…Hints have appeared in the literature, however, that suggest the trigeminal system may respond directly to light. Ablation of melanopsin-expressing neurons reduces corneal mechanical sensitivity and light aversion, suggesting that melanopsin influences the function of both Aδ and C fibers, respectively (Matynia et al, 2015 ). Furthermore, trigeminal blink reflexes are retained after optic nerve transection (Dolgonos et al, 2011 ) and bright light induces markers of neuronal activity in the trigeminal nucleus caudalis in rats (Okamoto et al, 2009 , 2010 ).…”

Section: Introductionmentioning

confidence: 99%

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Peripheral Sensory Neurons Expressing Melanopsin Respond to Light

Matynia

Nguyen

Sun

et al. 2016

Front. Neural Circuits

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The ability of light to cause pain is paradoxical. The retina detects light but is devoid of nociceptors while the trigeminal sensory ganglia (TG) contain nociceptors but not photoreceptors. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are thought to mediate light-induced pain but recent evidence raises the possibility of an alternative light responsive pathway independent of the retina and optic nerve. Here, we show that melanopsin is expressed in both human and mouse TG neurons. In mice, they represent 3% of small TG neurons that are preferentially localized in the ophthalmic branch of the trigeminal nerve and are likely nociceptive C fibers and high-threshold mechanoreceptor Aδ fibers based on a strong size-function association. These isolated neurons respond to blue light stimuli with a delayed onset and sustained firing, similar to the melanopsin-dependent intrinsic photosensitivity observed in ipRGCs. Mice with severe bilateral optic nerve crush exhibit no light-induced responses including behavioral light aversion until treated with nitroglycerin, an inducer of migraine in people and migraine-like symptoms in mice. With nitroglycerin, these same mice with optic nerve crush exhibit significant light aversion. Furthermore, this retained light aversion remains dependent on melanopsin-expressing neurons. Our results demonstrate a novel light-responsive neural function independent of the optic nerve that may originate in the peripheral nervous system to provide the first direct mechanism for an alternative light detection pathway that influences motivated behavior.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Peripheral Sensory Neurons Expressing Melanopsin Respond to Light

Matynia

Nguyen

Sun

et al. 2016

Front. Neural Circuits

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“…Another possible explanation for the presence of persistent corneal damage after cataract surgery may be involved altered corneal mechanosensitivity mediating intrinsically photosensitive retinal ganglion cells (ipRGCs) [24,25]. With the existence of melanopsin, ipRGCs respond to light in the absence of rod and cone photoreceptor input.…”

Section: Discussionmentioning

confidence: 99%

Persistently Worsened Tear Break-up Time and Keratitis in Unilateral Pseudophakic Eyes after a Long Postoperative Period

et al. 2020

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Dry eye disease may develop and persist after cataract surgery; however, unilateral cases have not been fully documented. This cross-sectional, observational study was conducted in five eye clinics in Japan. A total of 1023 outpatients were initially enrolled, and 89 unilateral pseudophakic subjects with 1+ year of follow-up after uncomplicated cataract surgery were included. The tear break-up times (TBUTs) and keratoconjunctival staining results were compared between phakic and pseudophakic eyes. The mean age of the patients was 69.3 ± 10.4 years (32 men, 36.0%), and the mean postoperative period was 4.6 ± 4.4 (1–20) years. For the ophthalmic parameters, the TBUTs were 4.4 ± 1.9 and 3.8 ± 1.9 s (p < 0.001), the keratoconjunctival staining scores were 0.11 ± 0.38 and 0.22 ± 0.56 (p = 0.02), the spherical equivalents were −1.27 ± 2.51 and −0.99 ± 1.45 D (p = 0.21), the astigmatic errors were 0.79 ± 0.66 and 0.78 ± 0.58 D (p = 0.80), and the intraocular pressures were 13.6 ± 2.9 and 13.5 ± 2.6 mmHg (p = 0.62) for the phakic and pseudophakic eyes, respectively. The corneal status was significantly worse in the pseudophakic eyes than in the contralateral phakic eyes, even after more than one year after implant surgery. The present results suggested that long-term ocular surface problems should be examined further since they may not originate only from surgery or postoperative ocular surface diseases.

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