scholarly journals TPC2 promotes choroidal angiogenesis and inflammation in a mouse model of neovascular age-related macular degeneration

2021 ◽  
Vol 4 (8) ◽  
pp. e202101047
Author(s):  
Yanfen Li ◽  
Christian Schön ◽  
Cheng-Chang Chen ◽  
Zhuo Yang ◽  
Raffael Liegl ◽  
...  
Keyword(s):  
Mouse Model ◽  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Immune Activation ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Strong Immune Response ◽  
Age Related ◽  
Key Factor ◽  
Photoreceptor Death

Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly and can be classified either as dry or as neovascular (or wet). Neovascular AMD is characterized by a strong immune response and the inadequate release of cytokines triggering angiogenesis and induction of photoreceptor death. The pathomechanisms of AMD are only partly understood. Here, we identify the endolysosomal two-pore cation channel TPC2 as a key factor of neovascularization and immune activation in the laser-induced choroidal neovascularization (CNV) mouse model of AMD. Block of TPC2 reduced retinal VEGFA and IL-1β levels and diminished neovascularization and immune activation. Mechanistically, TPC2 mediates cationic currents in endolysosomal organelles of immune cells and lack of TPC2 leads to reduced IL-1β levels in areas of choroidal neovascularization due to endolysosomal trapping. Taken together, our study identifies TPC2 as a promising novel therapeutic target for the treatment of AMD.

scholarly journals Age-Related Choroidal Atrophy and Choroidal Neovascularization

2017 ◽  
pp. 336-339
Keyword(s):  
Optical Coherence Tomography ◽  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Visual Function ◽  
Elderly Population ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Optical Coherence ◽  
Age Related

The choroid is a highly vascular, pigmented tissue located between the retina and sclera. The structure and thickness of choroid can be assessed by recently developed optical coherence tomography technologies. Age-related choroidal atrophy is a choroidal pathology that affects the elderly population and often accompanies and sometimes mimics age-related macular degeneration. Patients with age-related choroidal atrophy have a better visual function but have a higher risk of developing glaucoma.

scholarly journals CasRx-mediated RNA targeting prevents choroidal neovascularization in a mouse model of age-related macular degeneration

2020 ◽  
Vol 7 (5) ◽  
pp. 835-837 ◽  
Author(s):  
Changyang Zhou ◽  
Xinde Hu ◽  
Cheng Tang ◽  
Wenjia Liu ◽  
Shaoran Wang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Age Related Macular Degeneration ◽  
Proof Of Concept ◽  
Rna Transcripts ◽  
Age Related ◽  
Rna Targeting

Summary RNA-targeting CRISPR system Cas13 offers an efficient approach for manipulating RNA transcripts in vitro. In this perspective, we provide a proof-of-concept demonstration that Cas13-mediated Vegfa knockdown in vivo could prevent the development of laser-induced CNV in mouse model of Age-related macular degeneration.

scholarly journals Epigenetic hallmarks of age-related macular degeneration are recapitulated in a photosensitive mouse model

2020 ◽  
Vol 29 (15) ◽  
pp. 2611-2624
Author(s):  
Jennings Luu ◽  
Les Kallestad ◽  
Thanh Hoang ◽  
Dominik Lewandowski ◽  
Zhiqian Dong ◽  
...  
Keyword(s):  
Mouse Model ◽  
Macular Degeneration ◽  
Acute Stress ◽  
The Elderly ◽  
Causal Link ◽  
Chromatin Accessibility ◽  
Age Related Macular Degeneration ◽  
Light Damage ◽  
Photoreceptor Degeneration ◽  
Age Related

Abstract Age-related macular degeneration (AMD) is a chronic, multifactorial disorder and a leading cause of blindness in the elderly. Characterized by progressive photoreceptor degeneration in the central retina, disease progression involves epigenetic changes in chromatin accessibility resulting from environmental exposures and chronic stress. Here, we report that a photosensitive mouse model of acute stress-induced photoreceptor degeneration recapitulates the epigenetic hallmarks of human AMD. Global epigenomic profiling was accomplished by employing an Assay for Transposase-Accessible Chromatin using Sequencing (ATAC-Seq), which revealed an association between decreased chromatin accessibility and stress-induced photoreceptor cell death in our mouse model. The epigenomic changes induced by light damage include reduced euchromatin and increased heterochromatin abundance, resulting in transcriptional and translational dysregulation that ultimately drives photoreceptor apoptosis and an inflammatory reactive gliosis in the retina. Of particular interest, pharmacological inhibition of histone deacetylase 11 (HDAC11) and suppressor of variegation 3–9 homolog 2 (SUV39H2), key histone-modifying enzymes involved in promoting reduced chromatin accessibility, ameliorated light damage in our mouse model, supporting a causal link between decreased chromatin accessibility and photoreceptor degeneration, thereby elucidating a potential new therapeutic strategy to combat AMD.

scholarly journals CRISPR-LbCpf1 prevents choroidal neovascularization in a mouse model of age-related macular degeneration

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Taeyoung Koo ◽  
Sung Wook Park ◽  
Dong Hyun Jo ◽  
Daesik Kim ◽  
Jin Hyoung Kim ◽  
...  
Keyword(s):  
Mouse Model ◽  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Age Related Macular Degeneration ◽  
Age Related

Intravitreal Ets1 siRNA alleviates choroidal neovascularization in a mouse model of age-related macular degeneration

2019 ◽  
Vol 376 (3) ◽  
pp. 341-351 ◽  
Author(s):  
Manhui Zhu ◽  
Li Jiang ◽  
You Yuan ◽  
Lili Chen ◽  
Xiaojuan Liu ◽  
...  
Keyword(s):  
Mouse Model ◽  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Age Related Macular Degeneration ◽  
Age Related

scholarly journals CD59, a Complement Regulatory Protein, Controls Choroidal Neovascularization in a Mouse Model of Wet-Type Age-Related Macular Degeneration

2007 ◽  
Vol 178 (3) ◽  
pp. 1783-1790 ◽  
Author(s):  
Nalini S. Bora ◽  
Sankaranarayanan Kaliappan ◽  
Purushottam Jha ◽  
Qin Xu ◽  
Baalasubramanian Sivasankar ◽  
...  
Keyword(s):  
Mouse Model ◽  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Regulatory Protein ◽  
Age Related Macular Degeneration ◽  
Complement Regulatory Protein ◽  
Age Related

scholarly journals The Anti-Inflammatory Effect of Hydrogen Gas Inhalation and Its Influence on Laser-Induced Choroidal Neovascularization in a Mouse Model of Neovascular Age-Related Macular Degeneration

2021 ◽  
Vol 22 (21) ◽  
pp. 12049
Author(s):  
I-Chia Liang ◽  
Wen-Chin Ko ◽  
Yu-Jou Hsu ◽  
Yi-Ru Lin ◽  
Yun-Hsiang Chang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Macular Degeneration ◽  
Mrna Expression ◽  
Choroidal Neovascularization ◽  
Hydrogen Gas ◽  
Age Related Macular Degeneration ◽  
Fluorescence Angiography ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Age Related

Background: Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. Choroidal neovascularization (CNV) is the major pathologic feature of neovascular AMD. Oxidative damages and the ensuing chronic inflammation are representative of trigger events. Hydrogen gas (H2) has been demonstrated as an antioxidant and plays a role in the regulation of oxidative stress and inflammation. This experiment aimed to investigate the influence of H2 inhalation on a mouse model of CNV. Methods: Laser was used to induce CNV formation. C57BL/6J mice were divided into five groups: the control group; the laser-only group; and the 2 h, 5 h, and 2.5 h/2.5 h groups that received laser and H2 inhalation (21% oxygen, 42% hydrogen, and 37% nitrogen mixture) for 2 h, 5 h, and 2.5 h twice every day, respectively. Results: The severity of CNV leakage on fluorescence angiography showed a significant decrease in the H2 inhalation groups. The mRNA expression of hypoxia-inducible factor 1 alpha and its immediate downstream target vascular endothelial growth factor (VEGF) showed significant elevation after laser, and this elevation was suppressed in the H2 inhalation groups in an inhalation period length-related manner. The mRNA expression of cytokines, including tumor necrosis factor alpha and interlukin-6, also represented similar results. Conclusion: H2 inhalation could alleviate CNV leakage in a laser-induced mouse CNV model, and the potential mechanism might be related to the suppression of the inflammatory process and VEGF-driven CNV formation.

scholarly journals CasRx-mediated RNA targeting prevents choroidal neovascularization in a mouse model of age-related macular degeneration

2020 ◽  
Author(s):  
Changyang Zhou ◽  
Xinde Hu ◽  
Cheng Tang ◽  
Wenjia Liu ◽  
Shaoran Wang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Age Related Macular Degeneration ◽  
Adeno Associated Virus ◽  
Cleavage Activity ◽  
Age Related ◽  
Family Protein ◽  
Rna Targeting

AbstractThe smallest Cas13 family protein, CasRx, has a high cleavage activity and targeting specificity, offering attractive opportunity for therapeutic applications. Here we report that delivery of CasRx by adeno-associated virus via intravitreal injection could efficiently knockdown Vegfa transcripts and significantly reduce the area of laser-induced choroidal neovascularization in a mouse model of age-related macular degeneration. Thus, RNA-targeting CRISPR system could be used for in vivo gene therapy.

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