Lasagni Vitar Romina Mayra, Rama Paolo, Ferrari Giulio
Cornea and Ocular Surface Disease Unit, Eye Repair Lab, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Cornea and Ocular Surface Disease Unit, Eye Repair Lab, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Prog Retin Eye Res. 2022 Jan;86:100974. doi: 10.1016/j.preteyeres.2021.100974. Epub 2021 Jun 7.
Corneal nerves are instrumental to maintain cornea integrity through regulation of key physiological functions such as tear secretion, blink reflex, and neuropeptide turnover. Corneal nerve injury/stimulation can follow many insults including mechanical/chemical trauma, infections and surgeries. Nerve disruption initiates a process named neurogenic inflammation which leads to edema, pain, and recruitment and activation of leukocytes. Interestingly, leukocyte influx in the cornea can further damage nerves by releasing inflammatory mediators-including neuropeptides. The clinical outcome of neuroinflammation can be beneficial or detrimental to corneal integrity. On one side, it ensures prompt wound healing and prevents infections. On the other, prolonged and/or deranged neuroinflammation can permanently disrupt corneal integrity and impair vision. The cornea is an ideal site to study peripheral neuroinflammation and neurogenic inflammation since it receives the highest density of sensory nerves of the entire body. We will review the corneal nerve anatomy and neurochemistry, discuss the beneficial and detrimental effects of neurogenic inflammation in corneal wound healing, inflammatory processes, and pain. We will also examine the emerging remote impact of corneal nerve disruption on the trigeminal ganglion and the brain, highlighting the key role of neuropeptide Substance P. Finally, we will discuss the clinical relevance of such neuroinflammatory network in the context of severe and highly prevalent ocular diseases, including potential treatments.
角膜神经通过调节关键生理功能,如泪液分泌、眨眼反射和神经肽更新,对维持角膜完整性起着重要作用。角膜神经损伤/刺激可由多种损伤引起,包括机械/化学创伤、感染和手术。神经破坏引发一个名为神经源性炎症的过程,导致水肿、疼痛以及白细胞的募集和激活。有趣的是,角膜中的白细胞流入可通过释放包括神经肽在内的炎症介质进一步损伤神经。神经炎症的临床结果对角膜完整性可能有益也可能有害。一方面,它可确保伤口迅速愈合并预防感染。另一方面,长期和/或紊乱的神经炎症会永久性破坏角膜完整性并损害视力。角膜是研究外周神经炎症和神经源性炎症的理想部位,因为它拥有全身最高密度的感觉神经。我们将回顾角膜神经解剖学和神经化学,讨论神经源性炎症在角膜伤口愈合、炎症过程和疼痛中的有益和有害影响。我们还将研究角膜神经破坏对三叉神经节和大脑的新出现的远程影响,并强调神经肽P物质的关键作用。最后,我们将在严重且高度常见的眼部疾病背景下讨论这种神经炎症网络的临床相关性,包括潜在的治疗方法。