Gene therapy and transplantation in CNS repair: The visual system

Alan Harvey, Y. Hu, Simone Leaver, C. Mellough, K. Park, J. Verhaagen, Giles Plant, Q. Cui

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Normal visual function in humans is compromised by a range of inherited and acquired degenerative conditions, many of which affect photoreceptors and/or retinal pigment epithelium. As a consequence the majority of experimental gene- and cell-based therapies are aimed at rescuing or replacing these cells. We provide a brief overview of these studies, but the major focus of this review is on the inner retina, in particular how gene therapy and transplantation can improve the viability and regenerative capacity of retinal ganglion cells (RGCs). Such studies are relevant to the development of new treatments for ocular conditions that cause RGC loss or dysfunction, for example glaucoma, diabetes, ischaemia, and various inflammatory and neurodegenerative diseases. However, RGCs and associated central visual pathways also serve as an excellent experimental model of the adult central nervous system (CNS) in which it is possible to study the molecular and cellular mechanisms associated with neuroprotection and axonal regeneration after neurotrauma. In this review we present the current state of knowledge pertaining to RGC responses to injury, neurotrophic and gene therapy strategies aimed at promoting RGC survival, and how best to promote the regeneration of RGC axons after optic nerve or optic tract injury. We also describe transplantation methods being used in attempts to replace lost RGCs or encourage the regrowth of RGC axons back into visual centres in the brain via peripheral nerve bridges. Cooperative approaches including novel combinations of transplantation, gene therapy and pharmacotherapy are discussed. Finally, we consider a number of caveats and future directions, such as problems associated with compensatory sprouting and the reformation of visuotopic maps, the need to develop efficient, regulatable viral vectors, and the need to develop different but sequential strategies that target the cell body and/or the growth cone at appropriate times during the repair process. (c) 2006 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)449-489
JournalProgress in Retinal and Eye Research
Volume25
Issue number5
DOIs
Publication statusPublished - 2006

Fingerprint

Retinal Ganglion Cells
Genetic Therapy
Central Nervous System
Transplantation
Axons
Regeneration
Growth Cones
Visual Pathways
Retinal Pigment Epithelium
Wounds and Injuries
Optic Nerve
Cell- and Tissue-Based Therapy
Peripheral Nerves
Neurodegenerative Diseases
Glaucoma
Retina
Cell Survival
Theoretical Models
Ischemia
Drug Therapy

Cite this

Harvey, Alan ; Hu, Y. ; Leaver, Simone ; Mellough, C. ; Park, K. ; Verhaagen, J. ; Plant, Giles ; Cui, Q. / Gene therapy and transplantation in CNS repair: The visual system. In: Progress in Retinal and Eye Research. 2006 ; Vol. 25, No. 5. pp. 449-489.
@article{9b99c14ee73543f88c71fa00994912b6,
title = "Gene therapy and transplantation in CNS repair: The visual system",
abstract = "Normal visual function in humans is compromised by a range of inherited and acquired degenerative conditions, many of which affect photoreceptors and/or retinal pigment epithelium. As a consequence the majority of experimental gene- and cell-based therapies are aimed at rescuing or replacing these cells. We provide a brief overview of these studies, but the major focus of this review is on the inner retina, in particular how gene therapy and transplantation can improve the viability and regenerative capacity of retinal ganglion cells (RGCs). Such studies are relevant to the development of new treatments for ocular conditions that cause RGC loss or dysfunction, for example glaucoma, diabetes, ischaemia, and various inflammatory and neurodegenerative diseases. However, RGCs and associated central visual pathways also serve as an excellent experimental model of the adult central nervous system (CNS) in which it is possible to study the molecular and cellular mechanisms associated with neuroprotection and axonal regeneration after neurotrauma. In this review we present the current state of knowledge pertaining to RGC responses to injury, neurotrophic and gene therapy strategies aimed at promoting RGC survival, and how best to promote the regeneration of RGC axons after optic nerve or optic tract injury. We also describe transplantation methods being used in attempts to replace lost RGCs or encourage the regrowth of RGC axons back into visual centres in the brain via peripheral nerve bridges. Cooperative approaches including novel combinations of transplantation, gene therapy and pharmacotherapy are discussed. Finally, we consider a number of caveats and future directions, such as problems associated with compensatory sprouting and the reformation of visuotopic maps, the need to develop efficient, regulatable viral vectors, and the need to develop different but sequential strategies that target the cell body and/or the growth cone at appropriate times during the repair process. (c) 2006 Elsevier Ltd. All rights reserved.",
author = "Alan Harvey and Y. Hu and Simone Leaver and C. Mellough and K. Park and J. Verhaagen and Giles Plant and Q. Cui",
year = "2006",
doi = "10.1016/j.preteyeres.2006.07.002",
language = "English",
volume = "25",
pages = "449--489",
journal = "Progress in Retinal and Eye Research",
issn = "1350-9462",
publisher = "Pergamon",
number = "5",

}

Gene therapy and transplantation in CNS repair: The visual system. / Harvey, Alan; Hu, Y.; Leaver, Simone; Mellough, C.; Park, K.; Verhaagen, J.; Plant, Giles; Cui, Q.

In: Progress in Retinal and Eye Research, Vol. 25, No. 5, 2006, p. 449-489.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Gene therapy and transplantation in CNS repair: The visual system

AU - Harvey, Alan

AU - Hu, Y.

AU - Leaver, Simone

AU - Mellough, C.

AU - Park, K.

AU - Verhaagen, J.

AU - Plant, Giles

AU - Cui, Q.

PY - 2006

Y1 - 2006

N2 - Normal visual function in humans is compromised by a range of inherited and acquired degenerative conditions, many of which affect photoreceptors and/or retinal pigment epithelium. As a consequence the majority of experimental gene- and cell-based therapies are aimed at rescuing or replacing these cells. We provide a brief overview of these studies, but the major focus of this review is on the inner retina, in particular how gene therapy and transplantation can improve the viability and regenerative capacity of retinal ganglion cells (RGCs). Such studies are relevant to the development of new treatments for ocular conditions that cause RGC loss or dysfunction, for example glaucoma, diabetes, ischaemia, and various inflammatory and neurodegenerative diseases. However, RGCs and associated central visual pathways also serve as an excellent experimental model of the adult central nervous system (CNS) in which it is possible to study the molecular and cellular mechanisms associated with neuroprotection and axonal regeneration after neurotrauma. In this review we present the current state of knowledge pertaining to RGC responses to injury, neurotrophic and gene therapy strategies aimed at promoting RGC survival, and how best to promote the regeneration of RGC axons after optic nerve or optic tract injury. We also describe transplantation methods being used in attempts to replace lost RGCs or encourage the regrowth of RGC axons back into visual centres in the brain via peripheral nerve bridges. Cooperative approaches including novel combinations of transplantation, gene therapy and pharmacotherapy are discussed. Finally, we consider a number of caveats and future directions, such as problems associated with compensatory sprouting and the reformation of visuotopic maps, the need to develop efficient, regulatable viral vectors, and the need to develop different but sequential strategies that target the cell body and/or the growth cone at appropriate times during the repair process. (c) 2006 Elsevier Ltd. All rights reserved.

AB - Normal visual function in humans is compromised by a range of inherited and acquired degenerative conditions, many of which affect photoreceptors and/or retinal pigment epithelium. As a consequence the majority of experimental gene- and cell-based therapies are aimed at rescuing or replacing these cells. We provide a brief overview of these studies, but the major focus of this review is on the inner retina, in particular how gene therapy and transplantation can improve the viability and regenerative capacity of retinal ganglion cells (RGCs). Such studies are relevant to the development of new treatments for ocular conditions that cause RGC loss or dysfunction, for example glaucoma, diabetes, ischaemia, and various inflammatory and neurodegenerative diseases. However, RGCs and associated central visual pathways also serve as an excellent experimental model of the adult central nervous system (CNS) in which it is possible to study the molecular and cellular mechanisms associated with neuroprotection and axonal regeneration after neurotrauma. In this review we present the current state of knowledge pertaining to RGC responses to injury, neurotrophic and gene therapy strategies aimed at promoting RGC survival, and how best to promote the regeneration of RGC axons after optic nerve or optic tract injury. We also describe transplantation methods being used in attempts to replace lost RGCs or encourage the regrowth of RGC axons back into visual centres in the brain via peripheral nerve bridges. Cooperative approaches including novel combinations of transplantation, gene therapy and pharmacotherapy are discussed. Finally, we consider a number of caveats and future directions, such as problems associated with compensatory sprouting and the reformation of visuotopic maps, the need to develop efficient, regulatable viral vectors, and the need to develop different but sequential strategies that target the cell body and/or the growth cone at appropriate times during the repair process. (c) 2006 Elsevier Ltd. All rights reserved.

U2 - 10.1016/j.preteyeres.2006.07.002

DO - 10.1016/j.preteyeres.2006.07.002

M3 - Article

VL - 25

SP - 449

EP - 489

JO - Progress in Retinal and Eye Research

JF - Progress in Retinal and Eye Research

SN - 1350-9462

IS - 5

ER -