Gene Therapy Strategies for Glaucomatous Neurodegeneration

Title:Gene Therapy Strategies for Glaucomatous Neurodegeneration

Volume: 21 Issue: 5

Author(s): Rafael Lani-Louzada, Mariana Santana Dias, Rafael Linden, Vinicius Toledo Ribas and Hilda Petrs-Silva*

Affiliation:

• Laboratory of Neurogenesis, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro,Brazil

Keywords: Neuroprotection, neuroregeneration, glaucoma, rAAV, retinal ganglion cell, optic nerve.

Abstract: Glaucoma leads to irreversible vision loss and current therapeutic strategies are often insufficient to prevent the progression of the disease and consequent blindness. Elevated intraocular pressure is an important risk factor, but not required for the progression of glaucomatous neurodegeneration. The demise of retinal ganglion cells represents the final common pathway of glaucomatous vision loss. Still, lifelong control of intraocular pressure is the only current treatment to prevent severe vision loss, although it frequently fails despite best practices. This scenario calls for the development of neuroprotective and pro-regenerative therapies targeting the retinal ganglion cells as well as the optic nerve. Several experimental studies have shown the potential of gene modulation as a tool for neuroprotection and regeneration. In this context, gene therapy represents an attractive approach as a persistent treatment for glaucoma. Viral vectors engineered to promote overexpression of a broad range of cellular factors have been shown to protect retinal ganglion cells and/or promote axonal regeneration in experimental models. Here, we review the mechanisms involved in glaucomatous neurodegeneration and regeneration in the central nervous system. Then, we point out the current limitations of gene therapy platforms and review a myriad of studies that use viral vectors to manipulate genes in retinal ganglion cells, as a strategy to promote neuroprotection and regeneration. Finally, we address the potential of combining neuroprotective and regenerative gene therapies as an approach to glaucomatous neurodegeneration.

Cite this article as:

Lani-Louzada Rafael , Dias Santana Mariana , Linden Rafael, Ribas Toledo Vinicius and Petrs-Silva Hilda *, Gene Therapy Strategies for Glaucomatous Neurodegeneration, Current Gene Therapy 2021; 21 (5) . https://dx.doi.org/10.2174/1566523221666210126152000