Abstract: Primary glaucoma is a kind of multigenic complex hereditary disease affected by environmental factors. The gene therapy strategy for glaucoma can not correct or compensate for a single pathogenic gene only, but at present, gene therapy can still show “palliative” results such as actively delaying the onset, reducing or releasing symptoms. The current gene therapy strategies for glaucoma include gene therapy targeting the cytoskeleton regulatory protein of trabecular meshwork, gene therapy targeting the uveoscleral aqueous humor outflow channel, both of which mainly increase aqueous humor outflow and gene therapy targeting the ciliary epithelium, which mainly reduces aqueous humor production. In addition, anti-cicatricial gene therapy after trabecular surgery (such as transducing the metalloproteinase-3 gene into the operation area), retinal neuroprotective gene therapy [including improvement of retinal ganglion cell (RGC) nutrition by expressing brain-derived neurotrophic factor and activating neurotrophin receptor in the inner retina, exogenous expression of anti-apoptotic gene factors to antagonize RGC apoptosis, immune regulation to reduce RGC apoptosis, regulating glial cell function to support RGC, reducing reactive oxygen species (ROS), to antagonize RGC apoptosis, etc.]. However, the viral vectors still show risks more or less. It is an effective solution modifying the transgenic vectors to achieve accurate and specific targeted expression, which is also the key to promote the practicability of glaucoma gene therapy technology. In addition, how to maintain long-term expression and increase the effective therapeutic period is also a challenge for glaucoma gene therapy. (Ophthalmol CHN, 2022, 31: 1-7)

Key words: glaucoma, gene therapy