1. Taking Stock of Retinal Gene Therapy: Looking Back and Moving Forward
Jean Bennett 
Molecular Therapy 
Volume 25, Issue 5, Pages (May 2017)
DOI: /j.ymthe
Copyright © 2017 The American Society of Gene and Cell Therapy Terms and Conditions

2. Figure 1 Progress in Retinal Gene Therapy Depends on Knowing the Genes
The vertical arrow indicates the year that ASGCT was formed. Nineteen disease-causing genes had been identified. There are currently 256 known disease-causing genes (horizontal arrow).
Molecular Therapy  , DOI: ( /j.ymthe )
Copyright © 2017 The American Society of Gene and Cell Therapy Terms and Conditions

3. Figure 2
Frames from an Intra-operative Video Showing a Subretinal Injection in a Non-human Primate Retina
The injection cannula is advanced to the neural retina (A). When the syringe is pushed (B–E), fluid is pumped through the retinotomy made by the 39G injection cannula (arrow) into the subretinal space. (B–D) Arrowheads show the expanding bleb. (E) The cannula (arrow) is removed from the subretinal space. One can appreciate the fact that inner retinal blood vessels are raised over the “bleb” (D and E). The bright white circles are reflections from the corneal contact lens. Injection was carried out by A.M. Maguire, MD.
Molecular Therapy  , DOI: ( /j.ymthe )
Copyright © 2017 The American Society of Gene and Cell Therapy Terms and Conditions

4. Figure 3
Examples of Outcome Measures and Before-and-After Results from a Spark-Sponsored RPE65 Retinal Dystrophy Gene Therapy Clinical Trial
(A) Goldman visual fields show that the peripheral visual field increased after gene transfer while the area of the central scotoma (black region) decreased. (B) Pupillary light reflexes were absent when each eye (right, R; left, L) was illuminated with dim light (0.04 lux) prior to gene transfer, but were present in both eyes after bilateral delivery of AAV2-hRPE65v2. (C) Individual frames from videos of results from one subject of a multi-luminance mobility test carried out before and after bilateral gene transfer of AAV2-hRPE65v2 (Maguire et al., 2015, American Academy of Ophthalmology Retina Subspecialty Day, conference poster). The numbers in the upper left of “Before” panels indicate the time following start of the test for both the “Before” and “After” videos.
Molecular Therapy  , DOI: ( /j.ymthe )
Copyright © 2017 The American Society of Gene and Cell Therapy Terms and Conditions

5. Figure 4 Schemes for Retinal Gene Therapy
(A) Gene augmentation/replacement such as that used to ameliorate LCA due to RPE65 deficiency or achromatopsia due to CNGA3 deficiency requires presence of viable cells (although they may be sickly). (B) Gene augmentation/replacement may be used to attempt to halt progression of disease. This is one strategy being tested for choroideremia. The black spots represent tissue that has already died due to the disease and thus cannot be rescued. (C) Strategies with which to minimize environmental or genetic insults are shown. For example, delivery of decoy receptors or anti-angiogenic genes may halt or prevent neovascular complications in age-related macular degeneration. (D) Strategies may be used to harness the function of remaining cells in the retina in ways that they are normally not used. For example, optogenetic therapy may render retina with degenerated photoreceptors light sensitive. (E) Delivery of molecules that address the metabolic or nutritional deficits caused by disease may prolong the life and function of diseased cells. For example, neurotrophic factors such as rod-derived cone viability factor (RdCVF)135 or erythropoietin136 may extend the lives of the cells so that they can later benefit from therapy addressing the primary genetic flaw. (F) Nucleic acid-editing techniques may also prove useful in correcting specific mutations and/or segments of genes or in preventing damage caused by toxic gain-of-function mutations.
Molecular Therapy  , DOI: ( /j.ymthe )
Copyright © 2017 The American Society of Gene and Cell Therapy Terms and Conditions