Gene-agnostic therapeutic approaches for inherited retinal degenerations

被引：16

作者：

John, Molly C. C. ^{[1
]}

Quinn, Joel ^{[1
]}

Hu, Monica L. L. ^{[1
]}

Cehajic-Kapetanovic, Jasmina ^{[1
,2
]}

Xue, Kanmin ^{[1
,2
]}

机构：

[1] Univ Oxford, Nuffield Dept Clin Neurosci, Nuffield Lab Ophthalmol, Oxford, England

[2] Oxford Univ Hosp NHS Fdn Trust, Oxford Eye Hosp, Oxford, England

来源：

FRONTIERS IN MOLECULAR NEUROSCIENCE | 2023年 / 15卷

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会; 英国惠康基金;

关键词：

retina; medical therapies; inherited retinal degeneration; gene-independent; cellular reprogramming; stem cells; optogenetics; immune modulation; CILIARY NEUROTROPHIC FACTOR; OPTOGENETIC VISION RESTORATION; RESTORES VISUAL RESPONSES; PHOTORECEPTOR CELL-DEATH; PROMOTES CONE SURVIVAL; HUMAN MULLER GLIA; MOUSE MODEL; ROD PHOTORECEPTORS; ECTOPIC EXPRESSION; ANIMAL-MODELS;

D O I：

10.3389/fnmol.2022.1068185

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Inherited retinal diseases (IRDs) are associated with mutations in over 250 genes and represent a major cause of irreversible blindness worldwide. While gene augmentation or gene editing therapies could address the underlying genetic mutations in a small subset of patients, their utility remains limited by the great genetic heterogeneity of IRDs and the costs of developing individualised therapies. Gene-agnostic therapeutic approaches target common pathogenic pathways that drive retinal degeneration or provide functional rescue of vision independent of the genetic cause, thus offering potential clinical benefits to all IRD patients. Here, we review the key gene-agnostic approaches, including retinal cell reprogramming and replacement, neurotrophic support, immune modulation and optogenetics. The relative benefits and limitations of these strategies and the timing of clinical interventions are discussed.

引用

页数：22