Abstract
We systematically reviewed published translational research on gene-based therapy for retinal ganglion cell (RGC) neuroprotection. A search was conducted on Entrez PubMed on 23 December 2020 using the keywords “gene therapy”, “retinal ganglion cell” and “neuroprotection”. The initial search yielded 82 relevant articles. After restricting publications to those with full text available and in the English language, and then curating for only original articles on gene-based therapy, the final yield was 18 relevant articles. From the 18 papers, 17 of the papers utilized an adeno-associated viral (AAV) vector for gene therapy encoding specific genes of interest. Specifically, six of the studies utilized an AAV vector encoding brain-derived neurotrophic factor (BDNF), two of the studies utilized an AAV vector encoding erythropoietin (EPO), the remaining 10 papers utilized AAV vectors encoding different genes and one microRNA study. Although the literature shows promising results in both in vivo and in vitro models, there is still a significant way to go before gene-based therapy for RGC neuroprotection can proceed to clinical trials. Namely, the models of injury in many of the studies were more acute in nature, unlike the more progressive and neurodegenerative pathophysiology of diseases, such as glaucoma. The regulation of gene expression is also highly unexplored despite the use of AAV vectors in the majority of the studies reviewed. It is also expected that with the successful launch of messenger ribonucleic acid (mRNA)-based vaccinations in 2020, we will see a shift towards this technology for gene-based therapy in glaucoma neuroprotection.
Highlights
Glaucoma is the leading cause of global irreversible blindness and is generally categorized into two broad categories: open-angle and angle-closure glaucoma [1,2,3]
Retina ganglion cells (RGCs) are an important interventional target as glaucoma is characterized by optic nerve injury and the loss of RGCs [6]
From the 18 included papers, six of the studies utilized a viral vector encoding brainderived neurotrophic factor (BDNF), two of the studies utilized a viral vector encoding erythropoietin (EPO), and the remaining 10 papers focused on different viral vector encoded genes and one microRNA study
Summary
Glaucoma is the leading cause of global irreversible blindness and is generally categorized into two broad categories: open-angle and angle-closure glaucoma [1,2,3]. Current treatment strategies for open-angle glaucoma include medical, laser, or incisional methods to lower intraocular pressure (IOP) [4]. These current methods to lower IOP are proven to slow the progression of glaucoma-mediated damage and are neuroprotective in nature. As current available treatments only address IOP, for ischemic and traumatic optic neuropathies, this treatment strategy is unable to address or reverse neuropathic damage [2]. IOP-independent neuroprotective strategies would be beneficial for early stage intervention, potentially preventing disease progression, and reversal [4]. Retina ganglion cells (RGCs) are an important interventional target as glaucoma is characterized by optic nerve injury and the loss of RGCs [6]. The various etiologies of RGC death include defective axonal transport, ischemia, excitotoxicity, reactive oxygen species, trophic factor withdrawal, and loss of RGC electrical activity [4,7,8]
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