scholarly journals Therapeutic potential of translocator protein ligands for age-related macular degeneration

2022 ◽  
Vol 17 (4) ◽  
pp. 793
Author(s):  
Xinhua Shu ◽  
Xing Li ◽  
Zhiming He
2020 ◽  
Vol 12 (4) ◽  
pp. 35-41
Author(s):  
Kirill Yu. Gayduk ◽  
Sergey V. Churashov ◽  
Alexey N. Kulikov

Age-related macular degeneration (AMD) is the most common disease of the macula the area responsible for central vision. With regard to the pathogenesis of AMD, the main focus of most researchers is on the pathological processes occurring in the retinal pigment epithelium (RPE), which is considered as the main target of the disease. For the treatment of the dry form of the disease, which accounts for about 90% of all AMD cases, up to now no effective treatment methods were elaborated, while in the therapy of the wet form, antiangiogenic therapy, photodynamic therapy, and surgical treatment methods have been used with concrete success. Stem cells, possessing enormous therapeutic potential, are gradually being introduced into medical technologies, including ophthalmology. A number of pre-clinical studies have proven the safety of using cultured cells of the RPE, which gave rise to the beginning of clinical trials of the use of stem cells in the treatment of AMD patients. The review analyzes the data of scientific literature on the current understanding of the pathogenesis of AMD, pathogenetically substantiated therapies, including those using cell-based technologies, prospects and problems of using stem cells in the treatment of AMD patients.


2020 ◽  
Vol 245 (17) ◽  
pp. 1615-1625 ◽  
Author(s):  
Tanu Parmar ◽  
Joseph T Ortega ◽  
Beata Jastrzebska

Progressive retinal degeneration manifesting as age-related macular degeneration (AMD) in the elderly affects millions of individuals worldwide. Among various blinding diseases, AMD is the leading cause of central vision impairment in developed countries. Poor understanding of AMD etiology hampers the development of therapeutics against this devastating ocular disease. Currently, daily intravitreal injections of anti-angiogenic drugs, preventing abnormal vessel growth are the only treatment option for wet AMD. However, for dry AMD associated with retinal atrophy, at present there is no cure available. Recent clinical research has demonstrated beneficial effects of plant-derived compounds for various eye disorders. Thus, the ongoing efforts toward discovering efficient treatments preventing or delaying AMD progression focus on implementing a healthy diet rich in vitamins, including vitamin A, E, and C, minerals and carotenoids, in particular lutein and zeaxanthin, to reduce the disease burden. In addition, studies in cell culture and animal models indicated therapeutic potential of dietary polyphenolic compounds present in fruits and vegetables. These natural compounds protect visual function and retinal morphology likely due to their anti-oxidant and anti-inflammatory properties. Although understanding of the exact mechanism of these compounds’ positive effects requires further investigation, they provide non-invasive alternative to battle AMD-like condition. Additionally, studies carried in animal models mimicking AMD-like pathology, examining the pharmacological potential of particular retinoid analogs, demonstrated promising results for their use, and thus they should be considered as an option in developing therapies for AMD. In here, we summarize the most current knowledge regarding developments of therapeutic options to maintain ocular health and prevent vision loss associated with aging. Impact statement Age-related macular degeneration (AMD) is a devastating retinal degenerative disease. Epidemiological reports showed an expected increasing prevalence of AMD in the near future. The only one existing FDA-approved pharmacological treatment involves an anti-vascular endothelial growth factor (VEGF) therapy with serious disadvantages. This limitation emphasizes an alarming need to develop new therapeutic approaches to prevent and treat AMD. In this review, we summarize scientific data unraveling the therapeutic potential of the specific retinoid and natural compounds. The experimental results reported by us and other research groups demonstrated that retinoid analogs and compounds with natural product scaffolds could serve as lead compounds for the development of new therapeutic agents with potential to prevent or slow down the pathogenesis of AMD.


Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3066
Author(s):  
Fahad Farhan ◽  
Mohammad Almarhoun ◽  
Aileen Wong ◽  
Amy S. Findlay ◽  
Chris Bartholomew ◽  
...  

Cholesterol dysregulation has been implicated in age-related macular degeneration (AMD), the most common cause of visual impairment in the elderly. The 18 KDa translocator protein (TSPO) is a mitochondrial outer membrane protein responsible for transporting cholesterol from the mitochondrial outer membrane to the inner membrane. TSPO is highly expressed in retinal pigment epithelial (RPE) cells, and TSPO ligands have shown therapeutic potential for the treatment of AMD. Here, we characterized retinal pathology of Tspo knockout (KO) mice using histological, immunohistochemical, biochemical and molecular biological approaches. We found that Tspo KO mice had normal retinal morphology (by light microscopy) but showed elevated levels of cholesterol, triglycerides and phospholipids with perturbed cholesterol efflux in the RPE cells of Tspo KO mice. Expression of cholesterol-associated genes (Nr1h3, Abca1, Abcg1, Cyp27a1 and Cyp46a1) was significantly downregulated, and production of pro-inflammatory cytokines was markedly increased in Tspo KO retinas. Furthermore, microglial activation was also observed in Tspo KO mouse retinas. These findings provide new insights into the function of TSPO in the retina and may aid in the design of new therapeutic strategies for the treatment of AMD.


2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Sayan Ghosh ◽  
Archana Padmanabhan ◽  
Tanuja Vaidya ◽  
Alan M. Watson ◽  
Imran A. Bhutto ◽  
...  

Abstract Age-related macular degeneration (AMD) is an expanding problem as longevity increases worldwide. While inflammation clearly contributes to vision loss in AMD, the mechanism remains controversial. Here we show that neutrophils are important in this inflammatory process. In the retinas of both early AMD patients and in a mouse model with an early AMD-like phenotype, we show neutrophil infiltration. Such infiltration was confirmed experimentally using ribbon-scanning confocal microscopy (RSCM) and IFNλ− activated dye labeled normal neutrophils. With neutrophils lacking lipocalin-2 (LCN-2), infiltration was greatly reduced. Further, increased levels of IFNλ in early AMD trigger neutrophil activation and LCN-2 upregulation. LCN-2 promotes inflammation by modulating integrin β1 levels to stimulate adhesion and transmigration of activated neutrophils into the retina. We show that in the mouse model, inhibiting AKT2 neutralizes IFNλ inflammatory signals, reduces LCN-2-mediated neutrophil infiltration, and reverses early AMD-like phenotype changes. Thus, AKT2 inhibitors may have therapeutic potential in early, dry AMD.


2020 ◽  
Vol 30 ◽  
Author(s):  
Adhara de Queiroz Muradas ◽  
Juliana Vieira Figueiredo Urbano ◽  
Pablo Sousa de Oliveira ◽  
Senice Alvarenga Rodrigues Silva

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