Abstract
Purpose :
Light mediates reflexive behavior via optic nerve pathways such as the pupillary light reflex and trigeminal pathways such as the photic corneal blink reflex. Photoallodynia is a painful response induced or enhanced by light, common to many distinct ocular conditions from cone-dominant dystrophies to corneal injury to migraine. The contributions of the optic and trigeminal nerves to light and pain perception using light aversion, a surrogate for photoallodynia, was investigated.
Methods :
Light aversion behavior at 1000 lux was quantitated as an aversion index (AI: 0=no aversion; 1=complete aversion) in wild type (WT) mice and mice lacking rod and cone photoreceptors (Usher 1B, USH), in combination with optic nerve lesions (Optic Nerve Only – ONO, Trigeminal and Optic nerve, Artery and Sheath Transection – TOAST) or bilateral enucleation (BiLat). Nitroglycerin (NTG), a model for migraine, and morphine (MOR) were used to unmask light aversion. Acoustic startle was used to evaluate drug-induced acoustic hypersensitivity. Immunohistochemistry was used to evaluate retinal ganglion cells.
Results :
All mice with surgical lesions or enucleation exhibited minimal-to-no light aversion with vehicle. NTG-induced and MOR-induced light aversion in wild-type mice was highest in sham (NTG=0.81±0.06, n=12; MOR=0.88±0.06, n=14), and reduced after ONO (NTG=0.51±0.09, n=13; MOR=0.12±0.06, n=13), TOAST (NTG =0.22±0.13, n=8; MOR=0.63±0.13, n=8) and BiLat (NTG =0.01±0.04, n=6; MOR=0.55±0.12, n=6). USH mice have intact melanopsin-expressing retinal ganglion cells and normal drug-induced light aversion (NTG =0.87±0.04, n=20; MOR=0.78±0.06, n=20) that is significantly reduced after BiLat (NTG =0.25±0.08, n=10; MOR=0.22±0.09, n=10). NTG and MOR do not affect acoustic startle responses.
Conclusions :
Retinal-optic nerve pathways mediate light aversion in disease- and injury-free states. Trigeminal pathways are recruited in pathophysiological states and may represent a major component that signals light-induced or -enhanced pain. Acoustic stimuli do not further enhance light aversion, indicating distinct pathways from acoustic blink reflexes. NTG and MOR provide useful tools for identifying the neural circuit(s) underlying this latent light perception. Melanopsin expression has been observed in trigeminal ganglion neurons that respond to light ex vivo, providing a potential alternative circuit to influence light aversion.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.