Maryam Kheyrollah , Nicola Brandt , Anja U. Bräuer , Stefan Schrader , Sonja Mertsch
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引用次数: 0
Abstract
The integrity of corneal nerves is critical for ocular surface health, and damages can lead to Neurotrophic Keratopathy (NK). Despite the regenerative abilities of the peripheral nerve system (PNS), corneal nerve regeneration is often incomplete, and the underlying mechanisms are poorly understood. This study aims to identify potential factors that can enhance corneal nerve regeneration for NK treatment, with a focus on Lysophosphatidic acid (LPA).
Thus, the effect of LPA and its underlying pathways in nerve regeneration is investigated in detail using in vitro mouse sensory neurons. To elucidate the impact of LPA as well as to reveal the responsible receptor, several functional assays as well as siRNA-based knock-down experiments were conducted. Additionally, possible changes in underlying pathways were investigated on mRNA levels.
LPA-treated neurons significantly reduced fiber growth. However, LPAR2 knockdown neurons (Lpar2-KD) following LPA treatment showed a significant increase in fiber length. Additionally, LPA-treated neurons demonstrated enhanced levels of Lpar2 mRNA. On the other hand, nerve regeneration indicators such as Ngf, Gap-43, and Cdc42, along with LPA downstream signaling components like Pi3k and Ras, were elevated in Lpar2-KD neurons.
In conclusion, this study elucidates the inhibitory effects of LPA on fiber outgrowth of sensory neurons. Furthermore, LPAR2 was identified as the responsible receptor for the LPA effect. Thus, Lpar2 knockdown might be a promising therapeutic approach to enhance neuronal regeneration in patients with NK.
期刊介绍：
The Ocular Surface, a quarterly, a peer-reviewed journal, is an authoritative resource that integrates and interprets major findings in diverse fields related to the ocular surface, including ophthalmology, optometry, genetics, molecular biology, pharmacology, immunology, infectious disease, and epidemiology. Its critical review articles cover the most current knowledge on medical and surgical management of ocular surface pathology, new understandings of ocular surface physiology, the meaning of recent discoveries on how the ocular surface responds to injury and disease, and updates on drug and device development. The journal also publishes select original research reports and articles describing cutting-edge techniques and technology in the field.
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