Precision Medicine Trials in Retinal Degenerations

2021 ◽  
Vol 7 (1) ◽  
pp. 851-865
Author(s):  
Sarah R. Levi ◽  
Joseph Ryu ◽  
Pei-Kang Liu ◽  
Stephen H. Tsang
Keyword(s):  
Precision Medicine ◽  
Age Related Macular Degeneration ◽  
New Era ◽  
Base Editing ◽  
Retinal Degenerations ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies ◽  
Age Related ◽  
Molecular Therapies ◽  
Exciting Development

The beginning of the twenty-first century was marked by the innovative use of pharmacochemical interventions, which have since expanded to include gene-based molecular therapies. For years, treatment has focused on tackling the pathophysiology of monogenic orphan diseases, and one of the first applications of these novel genome editing technologies was the treatment of rare inherited retinal dystrophies. In this review, we present recent, ongoing, and future gene therapy–based treatment trials for choroideremia, X-linked retinitis pigmentosa, Stargardt disease, and age-related macular degeneration. As these trials pave the way toward halting the progression of such devastating diseases, we will begin to see the exciting development of newer, cutting-edge strategies including base editing and prime editing, ushering in a new era of precision medicine.

scholarly journals The Evolution of Fabrication Methods in Human Retina Regeneration

2021 ◽  
Vol 11 (9) ◽  
pp. 4102
Author(s):  
Beatrice Belgio ◽  
Anna Paola Salvetti ◽  
Sara Mantero ◽  
Federica Boschetti
Keyword(s):  
Cell Sheet ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Retinal Regeneration ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies ◽  
Age Related ◽  
Sight Loss ◽  
Cell Sheet Technology ◽  
Recent Trends

Optic nerve and retinal diseases such as age-related macular degeneration and inherited retinal dystrophies (IRDs) often cause permanent sight loss. Currently, a limited number of retinal diseases can be treated. Hence, new strategies are needed. Regenerative medicine and especially tissue engineering have recently emerged as promising alternatives to repair retinal degeneration and recover vision. Here, we provide an overview of retinal anatomy and diseases and a comprehensive review of retinal regeneration approaches. In the first part of the review, we present scaffold-free approaches such as gene therapy and cell sheet technology while in the second part, we focus on fabrication techniques to produce a retinal scaffold with a particular emphasis on recent trends and advances in fabrication techniques. To this end, the use of electrospinning, 3D bioprinting and lithography in retinal regeneration was explored.

scholarly journals Effects of A2E-Induced Oxidative Stress on Retinal Epithelial Cells: New Insights on Differential Gene Response and Retinal Dystrophies

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 307 ◽  
Author(s):  
Luigi Donato ◽  
Rosalia D’Angelo ◽  
Simona Alibrandi ◽  
Carmela Rinaldi ◽  
Antonina Sidoti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Genetic Diseases ◽  
Age Related Macular Degeneration ◽  
Retinal Cell ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies ◽  
Age Related

Oxidative stress represents one of the principal inductors of lifestyle-related and genetic diseases. Among them, inherited retinal dystrophies, such as age-related macular degeneration and retinitis pigmentosa, are well known to be susceptible to oxidative stress. To better understand how high reactive oxygen species levels may be involved in retinal dystrophies onset and progression, we performed a whole RNA-Seq experiment. It consisted of a comparison of transcriptomes’ profiles among human retinal pigment epithelium cells exposed to the oxidant agent N-retinylidene-N-retinylethanolamine (A2E), considering two time points (3h and 6h) after the basal one. The treatment with A2E determined relevant differences in gene expression and splicing events, involving several new pathways probably related to retinal degeneration. We found 10 different clusters of pathways involving differentially expressed and differentially alternative spliced genes and highlighted the sub- pathways which could depict a more detailed scenario determined by the oxidative-stress-induced condition. In particular, regulation and/or alterations of angiogenesis, extracellular matrix integrity, isoprenoid-mediated reactions, physiological or pathological autophagy, cell-death induction and retinal cell rescue represented the most dysregulated pathways. Our results could represent an important step towards discovery of unclear molecular mechanisms linking oxidative stress and etiopathogenesis of retinal dystrophies.

Retinal Prosthesis in the Treatment of Retinitis Pigmentosa

2021 ◽  
pp. 140-149
Keyword(s):  
Retinitis Pigmentosa ◽  
Retinal Prosthesis ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Cone Dystrophy ◽  
Research Groups ◽  
Retinal Prostheses ◽  
Retinal Degenerations ◽  
Age Related ◽  
Macular Diseases

Retinal prostheses are devices that receive an environmental visual stimulus, process it, and stimulate the degenerated retinal areas in order to produce a functionally efficient visual perception. Indications for implantation of these devices include hereditary retinal degenerations like retinitis pigmentosa, choroideremia, rod-cone dystrophy, and acquired macular diseases like geographic atrophy or fibrosis due to age-related macular degeneration. Clinically applied retinal prosthesis approaches can be classified as; epiretinal, subretinal, suprachoroidal, and scleral (transscleral suprachoroidal). In this paper, approaches of retinal prosthesis research groups, results of clinical trials, and the latest advances in their projects will be provided.

scholarly journals The Relevance of Oxidative Stress in the Pathogenesis and Therapy of Retinal Dystrophies

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 347 ◽  
Author(s):  
Elena B. Domènech ◽  
Gemma Marfany
Keyword(s):  
Oxidative Stress ◽  
Ganglion Cells ◽  
Age Related Macular Degeneration ◽  
Retinal Cell ◽  
Retinal Ganglion ◽  
Leber Hereditary Optic Neuropathy ◽  
Stress Effects ◽  
Retinal Dystrophies ◽  
Age Related ◽  
Stress Damage

Retinal cell survival requires an equilibrium between oxygen, reactive oxygen species, and antioxidant molecules that counteract oxidative stress damage. Oxidative stress alters cell homeostasis and elicits a protective cell response, which is most relevant in photoreceptors and retinal ganglion cells, neurons with a high metabolic rate that are continuously subject to light/oxidative stress insults. We analyze how the alteration of cellular endogenous pathways for protection against oxidative stress leads to retinal dysfunction in prevalent (age-related macular degeneration, glaucoma) as well as in rare genetic visual disorders (Retinitis pigmentosa, Leber hereditary optic neuropathy). We also highlight some of the key molecular actors and discuss potential therapies using antioxidants agents, modulators of gene expression and inducers of cytoprotective signaling pathways to treat damaging oxidative stress effects and ameliorate severe phenotypic symptoms in multifactorial and rare retinal dystrophies.

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