Gene Therapy for Leber Congenital Amaurosis

Bennett, Jean

doi:10.1002/0470092645.ch15

Cited by 18 publications

(12 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…LCA is one of the most severe forms of inherited retinal degeneration caused by mutations of retinal pigment epithelium protein of 65 kDa (RPE65) or lecithin-retinol acyltransferase (LRAT), two key enzymes involved in visual cycle (reviewed in Cremers et al, 2002; Bennett, 2004). Like Stargardt disease, LCA preferentially affects children starting from infancy, but results in more severe retinal dystrophy, typically with poor visual prognosis.…”

Section: Er Stress and Retinal Degenerationmentioning

confidence: 99%

Endoplasmic reticulum stress and the unfolded protein responses in retinal degeneration

Zhang

Sanders

Fliesler

et al. 2014

Experimental Eye Research

129

107

View full text Add to dashboard Cite

The endoplasmic reticulum (ER) is the primary intracellular organelle responsible for protein and lipid biosynthesis, protein folding and trafficking, calcium homeostasis, and several other vital processes in cell physiology. Disturbance in ER function results in ER stress and subsequent activation of the unfolded protein response (UPR). The UPR up-regulates ER chaperones, reduces protein translation, and promotes clearance of cytotoxic misfolded proteins to restore ER homeostasis. If this vital process fails, the cell will be signaled to enter apoptosis, resulting in cell death. Sustained ER stress also can trigger an inflammatory response and exacerbate oxidative stress, both of which contribute synergistically to tissue damage. Studies performed over the past decade have implicated ER stress in a broad range of human diseases, including neurodegenerative diseases, cancer, diabetes, and vascular disorders. Several of these diseases also entail retinal dysfunction and degeneration caused by injury to retinal neurons and/or to the blood vessels that supply retinal cells with nutrients, trophic and homeostatic factors, oxygen, and other essential molecules, as well as serving as a conduit for removal of waste products and potentially toxic substances from the retina. Collectively, such injuries represent the leading cause of blindness world-wide in all age groups. Herein, we summarize recent progress on the study of ER stress and UPR signaling in retinal biology and discuss the molecular mechanisms and the potential clinical applications of targeting ER stress as a new therapeutic approach to prevent and treat neuronal degeneration in the retina.

show abstract

Section: Er Stress and Retinal Degenerationmentioning

confidence: 99%

Endoplasmic reticulum stress and the unfolded protein responses in retinal degeneration

Zhang

Sanders

Fliesler

et al. 2014

Experimental Eye Research

129

107

View full text Add to dashboard Cite

show abstract

“…To date, therapeutic possibilities for IRD are limited. Nevertheless, a few treatment approaches have shown promise, such as: RPE65 gene replacement therapy for Leber’s congenital amaurosis (LCA) [2,3,4,5], genetic targeting of bipolar and/or ganglion cells with engineered photo-gates [6] or light-sensitive proteins such as channelrhodopsin-2 [7], exploitation of the protective effect of the neurotrophic factor [8], and microelectronic retinal prostheses [9,10]. …”

Section: Introductionmentioning

confidence: 99%

Early Visual Symptom Patterns in Inherited Retinal Dystrophies

et al. 2011

View full text Add to dashboard Cite

The present retrospective study compared initial visual symptom patterns in inherited retinal dystrophies (IRD) on the basis of records of 544 patients diagnosed with a wide variety of IRD at the Tuebingen University Eye Hospital from 2005 to 2008. Age at first onset of symptoms was noted, and the following clinical data were analyzed: visual acuity (VA), night vision disturbances, photophobia, onset of visual field defects, best corrected VA, and types of visual field defects. Median age at visual symptom onset was defined with 25th and 75th percentiles and compared in 15 IRD types. The main trends in VA changes in retinitis pigmentosa and cone-rod dystrophies were identified. This study was the first to combine disease history and clinical data analysis in such a wide variety of IRD. It showed that patterns of initial symptoms in IRD can provide extra clues for early differential diagnosis and inclusion of IRD patients in clinical trials.

show abstract

“…1,2 Because they are terminally differentiated and do not reenter the cell cycle for regeneration, photoreceptors that are lost cannot be replenished. The importance of photoreceptors to vision has spurred a spectrum of investigations ranging from photoreceptor rescue by trophic factors, 3 supporting cells, 4,5 or stem cells 6 to photoreceptor replacement through retinal regeneration [7][8][9] and transplantation. 10,11 The recent demonstration of successful photoreceptor transplantation in blind mice 12 offers hope for vision rescue or restoration through cell replacement.…”

mentioning

confidence: 99%