中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (1): 92-99.doi: 10.4103/1673-5374.375319

• 综述:视神经损伤修复保护与再生 • 上一篇    下一篇

青光眼基因治疗的概念——尚未实现的梦想

  

  • 出版日期:2024-01-15 发布日期:2023-08-02

The concept of gene therapy for glaucoma: the dream that has not come true yet

Robert Sulak1, Xiaonan Liu1, 2, Adrian Smedowski1, 3, *   

  1. 1Department of Physiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia in Katowice, Katowice, Poland; 2Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland; 3GlaucoTech Co., Katowice, Poland
  • Online:2024-01-15 Published:2023-08-02
  • Contact: Adrian Smedowski, MD, PhD, asmedowski@sum.edu.pl.
  • Supported by:
    This work was supported by Medical University of Silesia research grants, No. PCN-1-129/N/2/0 (to AS).

摘要: https://orcid.org/0000-0001-8528-955X (Adrian Smedowski); https://orcid.org/0000-0002-9600-0536 (Xiaonan Liu)

Abstract: Gene therapies, despite of being a relatively new therapeutic approach, have a potential to become an important alternative to current treatment strategies in glaucoma. Since glaucoma is not considered a single gene disease, the identified goals of gene therapy would be rather to provide neuroprotection of retinal ganglion cells, especially, in intraocular-pressure-independent manner. The most commonly reported type of vector for gene delivery in glaucoma studies is adeno-associated virus serotype 2 that has a high tropism to retinal ganglion cells, resulting in long-term expression and low immunogenic profile. The gene therapy studies recruit inducible and genetic animal models of optic neuropathy, like DBA/2J mice model of high-tension glaucoma and the optic nerve crush-model. Reported gene therapy-based neuroprotection of retinal ganglion cells is targeting specific genes translating to growth factors (i.e., brain derived neurotrophic factor, and its receptor TrkB), regulation of apoptosis and neurodegeneration (i.e., Bcl-xl, Xiap, FAS system, nicotinamide mononucleotide adenylyl transferase 2, Digit3 and Sarm1), immunomodulation (i.e., Crry, C3 complement), modulation of neuroinflammation (i.e., erythropoietin), reduction of excitotoxicity (i.e., CamKIIα) and transcription regulation (i.e., Max, Nrf2). On the other hand, some of gene therapy studies focus on lowering intraocular pressure, by impacting genes involved in both, decreasing aqueous humor production (i.e., aquaporin 1), and increasing outflow facility (i.e., COX2, prostaglandin F2α receptor, RhoA/RhoA kinase signaling pathway, MMP1, Myocilin). The goal of this review is to summarize the current state-of-art and the direction of development of gene therapy strategies for glaucomatous neuropathy.

Key words: adeno-associated virus, gene editing, gene therapy, glaucoma, IOP lowering, IOP-independent mechanisms, neuroprotection, optic nerve, optic neuropathy, retinal ganglion cells