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

作　　者：Robert Sulak Xiaonan Liu Adrian Smedowski 

机构地区：[1]Department of Physiology,Faculty of Medical Sciences in Katowice,Medical University of Silesia in Katowice,Katowice,Poland [2]Institute of Biotechnology,HiLIFE,University of Helsinki,Helsinki,Finland [3]GlaucoTech Co.,Katowice,Poland

出　　处：《Neural Regeneration Research》2024年第1期92-99,共8页中国神经再生研究（英文版）

基　　金：supported by Medical University of Silesia research grants,No.PCN-1-129/N/2/O(to AS)。

摘　　要：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 tro pism to retinal ganglion cells,res ulting in long-term expression and low immunogenic profile.The gene thera py 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.,e rythropoietin),reduction of excitotoxicity(i.e.,Com KIlα)and transcription regulation(i.e.,Max,Nrf2).On the other hand,some of gene therapy studies focus on lowering intra ocular pressure,by impacting genes involved in both,decreasing aqueous humor production(i.e.,aquaporin 1),and increasing outflow facility(i.e.,COX2,prostaglandin F2a receptor,RhoA/RhoA kinase signaling pathway,MMP1,Myocilin).The goal of this review is to summarize the current stateof-art and the direction of development of gene therapy strategies for glaucomatous neuropathy.

关 键 词：adeno-associated virus gene editing gene therapy GLAUCOMA IOP lowering IOP-independent mechanisms NEUROPROTECTION optic nerve optic neuropathy retinal ganglion cells 

分 类 号：R775[医药卫生—眼科] R450[医药卫生—临床医学]