Emerging Gene Manipulation Strategies for the Treatment of Monogenic Eye Disease

Purpose: The purpose of this study was to investigate the chemotaxis effect of stromal cell-derived factor-1 (SDF-1) on human adipose-derived stem cells (hADSCs). Methods: A lentivirus vector with the enhanced green fluorescent protein gene was constructed and transfected to hADSCs. A control group and an SDF-1 induction group were set to estimate the efficacy of SDF-1 in promoting hADSCs chemotaxis and migration. Results: After 7 days of infection with hADSCs by enhanced green fluorescent protein lentivirus, the positive rate of fluorescence expression detected by flow cytometry was 100%. After the addition of SDF-1 induction, the invasion ability of hADSCs was enhanced. Conclusions: SDF-1 can promote hADSCs migration and chemotaxis, which may play a role in stem cell transplantation.

Section: Discussionmentioning

confidence: 99%

Section: Sdf-1mentioning

confidence: 99%

Study on the Promotion of hADSCs Migration and Chemotaxis by SDF-1

Chen

2023

“…Gene manipulation, new approaches using epigenetics and degenerative retinal diseases, and retinal organoids in treating retinal diseases are not covered in this special issue but have good potential applications in the future. [9][10][11][12][13]…”

mentioning

confidence: 99%

Advances in Diagnosis and Therapy of Retinal Diseases

Jonas

Lam

2023

T his issue of the Asia-Pacific Journal of Ophthalmology (APJO) includes a series of articles on recent advances in the diagnosis and therapy of retinal diseases, written by leading experts in the field. Arrigo, Aragona, and Bandello address the role of inflammation in nonexudative and exudative age-related macular degeneration (AMD), which is characterized by various proinflammatory stimuli and involvement of proinflammatory or inflammatory cells and mediators including biochemical pathways. 1 The results of recent basic science and clinical studies paved the way to develop intravitreal medical therapies as an attempt to treat nonexudative (dry) AMD, or at least to reduce its progression. 1 Improvements in imaging techniques to visualize the surface and deeper structures of ocular tissue, in particular of the retinal and optic nerve, have revolutionized clinical and scientific ophthalmology, mainly through the clinical introduction of optical coherence tomography and OCT-based angiography. These noninvasive techniques with a spatial resolution of up to 1 µm allowed a markedly deeper understanding of the etiology and pathogenesis of ocular diseases and a profound improvement in their diagnosis, and in particular, an improvement in their monitoring for early detection of progression. Szeto et al 2 describe in this APJO issue recent advances in clinical applications of these imaging methods for retinal diseases. In particular, they refer to multimodal retinal imaging methods, such as ultra-widefield fundus angiography, in addition to fundus autofluorescence besides OCT and OCT-based angiography. The diseases covered include AMD, polypoidal choroidal vasculopathy, diabetic macular edema, central serous chorioretinopathy, retinal vein occlusion, and uveitis.The latest developments in exploring the genetic background of major retinal diseases are presented by Chen et al. 3 They discuss the application of candidate gene mutational and association analyses, linkage analysis, genome-wide association studies, transcriptome analysis, next-generation sequencing including targeted deep sequencing, whole exome sequencing, and whole genome sequencing. The application of these technologies resulted in the identification of a panoply of genes. Future studies will be directed to validate individual genes and to develop polygenic risk markers for the major retinal diseases. The use of artificial intelligence may further help in the advanced analysis of genetic and lifestyle data for the establishment of predictive factors for the risk of the onset, progression, and prognosis of retinal diseases. It will be a step in the direction to individualized precision medicine.Although perimetry belongs to the oldest techniques applied in clinical ophthalmology, direct fundus microperimetry has only recently been used on a larger scale for scientific and clinical purposes in retinology. 4 As described by Hori and colleagues, microperimetry together with modern imaging techniques, can provide insights into the physiology and pathology of macu...

“…The clinical trials currently registered for monogenic eye diseases are summarized by Burgess et al in their article in this issue. The 60 trials described show not only the speed with which research findings are being translated into clinical reality but also the hope that many patients may soon have treatments available 5. The most successful gene therapy for RP so far has been the subretinal application of voretigene neparvovec-rzyl (Luxturna) for the treatment of the RPE65 mutation-associated type of retinal dystrophy 6.…”

mentioning

confidence: 99%

“…The 60 trials described show not only the speed with which research findings are being translated into clinical reality but also the hope that many patients may soon have treatments available. 5 The most successful gene therapy for RP so far has been the subretinal application of voretigene neparvovec-rzyl (Luxturna) for the treatment of the RPE65 mutation-associated type of retinal dystrophy. 6 This therapy improves vision and follow-up data so far have shown an effect lasting for at least 4 years.…”

mentioning

confidence: 99%

Regenerative Medicine, Advanced Stem Cell, and Gene Therapies for Eye Diseases

Barnstable

Jonas

Zhang

2022

O cular disorders are among the most prevalent diseases worldwide and rank highly in the list of disabilityassociated life years as assessed in the Global Burden of Disease (GBD) study. 1 The revolution in cell and molecular biology over recent decades has provided a new palette with which to identify, study, and treat many ocular diseases. This special issue captures some of the advances in this area and points out directions that will undoubtedly change ophthalmology practice in the coming years.One of the most important advances has been the ability to use genetic analysis to identify disease-causing variants or risk factors. Initially microarray analysis, but now more commonly direct sequencing has provided a wealth of information about many ocular diseases. Perhaps the clearest example of this comes from many studies of diseases of the retinitis pigmentosa (RP) group. Although less common than many other ocular diseases, RP diseases as monogenetic disorders have the advantage for genetic studies of being transmitted in a Mendelian fashion. Autosomal dominant, autosomal recessive and X-linked forms of the diseases have been identified. To date, more than 70 loci (and more than 70 identified genes) have been detected as underlying causes for various forms of RP. If we include the broader range of retinopathies, the current number of identified loci is around 361 (with roughly 280 identified genes). 2 Identification of genes responsible for inherited eye diseases has often been a collaborative effort. In the article by Iwata and colleagues, the development of a consortium, initially in Japan but then becoming the Asian Eye Genetics Consortium and finally the Global Eye Genetics Consortium, 3 describes how it has been possible for 200 members in 30 countries to collect, identify, and catalog samples on a global scale. 4 Examination of the list of gene mutations that can cause RP is both gratifying that this knowledge can often allow patients to get a precise diagnosis of their disease, but also disturbing because it suggests that each mutation needs a different treatment. The clinical trials currently registered for monogenic eye diseases are summarized by Burgess et al in their article in this issue. The 60 trials described show not only the speed with which research findings are being translated into clinical reality but also the hope that many patients may soon have treatments available. 5 The most successful gene therapy for RP so far has been the subretinal application of voretigene neparvovec-rzyl (Luxturna) for the treatment of the RPE65 mutation-associated type of retinal dystrophy. 6 This therapy improves vision and follow-up data so far have shown an effect lasting for at least 4 years. 7 In the article by McLenachan et al 8 in this issue, a different inherited disease, Usher Syndrome Type IIA, is discussed including an overview of treatments currently in clinical trials. One of the remaining problems of gene therapy is that of dosing. Too little of a gene may be ineffective and too much may be toxic. ...