title: Gene therapy for diabetic retinopathy: Are we ready to make the leap from bench to bedside?
abstract: Diabetic retinopathy (DR), a chronic and progressive complication of diabetes mellitus, is a sight-threatening disease characterized in the early stages by neuronal and vascular dysfunction in the retina, and later by neovascularization that further damages vision. A major contributor to the pathology is excess production of vascular endothelial growth factor (VEGF), a growth factor that induces formation of new blood vessels and increases permeability of existing vessels. Despite the recent availability of effective treatments for the disease, including laser photocoagulation and therapeutic VEGF antibodies, DR remains a significant cause of vision loss worldwide. Existing anti-VEGF agents, though generally effective, are limited by their short therapeutic half-lives, necessitating frequent intravitreal injections and the risk of attendant adverse events. Management of DR with gene therapies has been proposed for several years, and pre-clinical studies have yielded enticing findings. Gene therapy holds several advantages over conventional treatments for DR, such as a longer duration of therapeutic effect, simpler administration, the ability to intervene at an earlier stage of the disease, and potentially fewer side-effects. In this review, we summarize the current understanding of the pathophysiology of DR and provide an overview of research into DR gene therapies. We also examine current barriers to the clinical application of gene therapy for DR and evaluate future prospects for this approach.
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Jiang-Hui
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia; Discipline of Ophthalmology, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Damien
authors.initials: D
authors.lastname: Ling
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Tu
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: van Wijngaarden
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dusting
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia; Menzies Institute for Medical Research, University of Tasmania, Tasmania, Australia. Electronic address: rickliu0817@gmail.com.
authors.forename: Guei-Sheung
authors.initials: GS
authors.lastname: Liu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D003930:Diabetic Retinopathy / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D044127:Epigenesis, Genetic; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A
keywords: Diabetic macular edema; Diabetic retinopathy; Gene therapies; Neuronal degeneration; Vascular dysfunction; Vascular endothelial growth factor