Advances in Glaucoma Treatment and Management: Gene Therapy
Advances in Glaucoma Treatment and Management: Gene Therapy
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DOI：
10.1167/iovs.12-9483o
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发表时间：
2012-05-01
影响因子：
4.4
通讯作者：
Borras, Terete
中科院分区：
文献类型：
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作者：
Borras, Terete
青光眼的特征在于视网膜神经节细胞（RGC）的死亡和视力丧失。它是世界上第二大最常见的不可逆失明原因，主要影响老年人。1患病率预测显示，到2020年，全球估计将有7960万青光眼患者，其中女性比例高于男性。1青光眼可以治疗，但尚未治愈。目前可用的治疗方法，如每日滴眼液，导致高水平的不依从性，特别是在老年人群中。在包括我们在内的几个实验室里，正在进行紧张的研究，以寻找这种疾病的替代疗法。利用基因，我们寻求开发基因药物疗法，它比传统药物有效许多倍，并且允许更少的给药频率-也许每1或2年一次。在由隐性或显性基因引起的遗传性青光眼的情况下，我们寻求基因替换和基因敲除策略，可以逆转突变的不良结果。这种新的最先进的治疗技术目前已经可用，并已成功应用于其他疾病，包括眼部疾病。2大多数青光眼是由小梁网（trans小梁网，TM）组织功能障碍引起的，这反过来又导致对房水流出的阻力增加和眼内压（IOP）升高。升高的IOP损害后部RGC的机制尚不完全清楚。升高的IOP是否首先损害RGC轴突然后导致细胞体死亡或者它首先损害细胞体然后导致轴突死亡是一个激烈讨论的主题。虽然眼压升高不是导致RGC死亡的唯一因素，但它是最常见的。所有目前可用的降低IOP的药物都能减缓所有青光眼的进展，即使是正常眼压性青光眼。
Glaucoma is characterized by the death of retinal ganglion cells (RGCs) and loss of vision. It is the second most frequent cause of irreversible blindness in the world and affects primarily the older population. 1 Projections of prevalence show that by 2020 there will be an estimated 79.6 million people worldwide with glaucoma, with a higher proportion of women than men. 1 Glaucoma can be treated but is not yet curable. Treatments currently available, such as the daily administration of eye drops, lead to high levels of noncompliance, especially in the aged population. In several laboratories, including ours, intense research is ongoing to search for alternative treatments of the disease. Using genes, we seek to develop gene drug therapies that can be many times more efficient than conventional drugs and allow less frequent administration—perhaps just once every 1 or 2 years. In cases of inherited glaucoma caused by either recessive or dominant genes, we seek gene replacement and gene knockdown strategies that could reverse the undesired outcome of the mutation. Technology for this new state-of-the-art treatment is currently available and has been successfully applied in other diseases, including conditions in the eye. 2Most glaucomas are induced by dysfunction of the trabecular meshwork (TM) tissue, which in turn leads to increased resistance to aqueous humor outflow and elevated intraocular pressure (IOP). The mechanism by which elevated IOP damages the posterior RGCs is not fully understood. Whether the elevated IOP first damages the RGC axons and then causes the cell body to die or it damages the cell body first, which then causes the axons to die is a subject of intense deliberation. Although elevated IOP is not the only factor causing RGC death, it is the most common. All currently available drugs that lower IOP slow the progression of all glaucomas, even the form referred to as normal-tension glaucoma.