iPRGCs介导的眼睑痉挛患者畏光神经环路研究

Photophobia is one of the most common symptoms of BEB patients, mainly manifested as intolerance to normal light, ocular discomfort, blinking. Currently, pathogenesis of BEB photophobia is unknown. The direct cause of photophobia is light, while the photoreceptor cells in the human eye is the first step to receive light stimulation. Numerous Studies have found that ipRGCs may be the main photosensitive cells involved in photophobia. Our previous clinical study confirmed that filtering the ipRGCs-specific spectral peak absorbance of 480nm wavelength light significantly improved the symptoms of patients with BEB, suggesting that ipRGCs is closely related to the occurrence and development BEB photophobia. Therefore, clarify downstream neuronal circuit of ipRGCs will help us further explore the mechanism of BEB photophobia and related therapeutic targets. It has been suggested that the thalamus may be a key part of the light-ipRGCs-blink circuit, and we speculate that ipRGCs may induce blinking through the optic nerve-thalamic-cortex -midbrain blink reflex circuit, but its specific neural circuit is unknown. Based on this, we are going to: 1. To clarify key nucleus (such as the thalamic Po dorsal nucleus, thalamic VA VL area, striatum, substantial nigral reticular, etc.) that are involved in the light stimulation -ipRGCs-blink circuit ; 2. To clarify specific projections of the light stimulation -ipRGCs-blink neural circuit; 3. Using functional magnetic resonance imaging to determine whether abnormalities occur in the above-mentioned pathway in patients with BEB photophobia..ipRGCs have a projection relationship with the regions related to thalamic pain. In addition, over-activation of the thalamic-related nuclei may increase blink reflex caused by increased input of the motor cortex to the facial nucleus. Therefore, spatial structure proximity and concomitant of photophobia (pain and blink reflexes always accompany) suggest that ipRGCs-pain-blinks may be linked by the same pathway. Therefore, based on this, we are going to further explore the following: (1) To study if light-stimulated ipRGCs-thalamic pain pathway could further induce blink? (2) On the basis of (1) To clarify that the specific site of the correlation between light-stimulated ipRGCs-thalamic pain pathways and blink reflex; (3) On the basis of (2), to clarify that specific projection of the pain-blink neural circuit and (4) Using functional magnetic resonance imaging to determine whether abnormalities occur in the above-mentioned pathway in patients with BEB photophobia.

畏光常见于BEB患者，表现为对正常光线的不耐受，出现眼部不适，瞬目增多，可诱发并加重眼睑痉挛。目前BEB畏光机制不明且缺乏有效治疗手段。我们的前期研究及其他研究均证实，人眼内一类特殊感光细胞ipRGCs与BEB畏光发生密切相关。因此明确ipRGCs通过何种环路引发瞬目将有助于进一步探索BEB畏光的发生机制及相关治疗靶点。研究提示，丘脑可能为光－ipRGCs－瞬目环路中的关键部位，我们推测，ipRGCs可能通过视神经－丘脑－皮层－中脑面神经核瞬目反射环路诱发瞬目，但其具体神经环路未知。因此，本课题将：1、明确关键核团（如丘脑Po背侧核团、丘脑VA区 VL区、纹状体、黑质网状部等）是否参与了光刺激－ipRGCs－瞬目环路；2、明确光刺激－ipRGCs－瞬目环路的具体投射走行；3、利用功能磁共振技术明确BEB患者脑内上述神经环路是否出现异常，从而了解BEB畏光发生的可能机制及潜在的治疗靶点。

黑色素细胞可能参与特发性孤立性眼睑痉挛患者畏光的病理生理学。我们评估了阻断黑素吸收波长以减少眼睑痉挛眨眼的效果，作为畏光症的可能替代品。本项目对21名参与者（11名眼睑痉挛者和10名健康对照者）进行研究。有三个测试：（1）在没有干预的情况下测量眨眼率（BR）的基线条件；（2） 两个条件，其中参与者在不佩戴研究镜片的情况下接受高强度或低强度的间歇性光刺激；(3)参与者在佩戴时接受高强度间歇性光刺激的四种情况,四种不同镜片之一：带中性灰色或FL-41的有色镜片，或阻挡480nm或590 nm的涂层镜片-nm波长。主要结果指标是BR。结果：在昏暗的房间条件下，眼睑痉挛组比对照组眨眼更频繁。与对照组相比，根据问卷调查，患者报告了更高的光敏性间歇性光刺激。当使用480nm和590nm阻挡透镜时，两组的BR均降低。在里面480nm和590nm阻挡透镜的患者的平均BR分别降低了9.6眨眼/分钟和10.3眨眼/分钟，而在对照组，平均BR分别下降4.4眨眼/分钟和4.3眨眼/分钟。结论：眼睑痉挛患者在光刺激下BR增加，随着590 nm和480 nm，BR降低-nm阻挡透镜。480nm和590nm涂层镜片可能在治疗中具有治疗潜力的最佳生物标志物。研究结果也提示了畏光的相关可能神经环路。