视网膜色素上皮细胞中REP-1的丧失导致了化体处理受损,并改变了 lysosomal通路的功能
Rita Coelho1, Pedro Antas1, Ana Fragoso Fonseca1
1iNOVA4Health, NOVA Medical School Universidade NOVA de Lisboa, Lisbon, Portugal 1169.
Molecular biology of the cell
|August 6, 2025
概括
胆血症 (CHM) 涉及由于CHM基因突变影响Rab护送蛋白-1 (REP-1) 的视网膜退化. 失去REP-1会损害溶酶体的功能,导致视力丧失.
科学领域:
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
- 眼科医生 眼科 眼科
背景情况:
- 胆血症 (CHM) 是一种罕见的遗传性视网膜退化症.
- 它源于CHM基因的突变,这对Rab护航蛋白-1 (REP-1) 功能至关重要.
- 在CHM中受到影响的特定细胞通路中REP-1的作用尚未完全理解.
研究的目的:
- 为了研究底层的细胞机制 胆血症.
- 为了确定REP-1缺乏如何影响视网膜色素表皮 (RPE) 细胞中的溶酶体通路和酶体处理.
主要方法:
- 利用CRISPR/Cas9敲除ARPE-19和诱导多能干细胞 (iPSC) 衍生的RPE细胞中的CHM基因.
- 使用显微镜和生物化学分析分析了溶酶体数量,甲素和BSA-Gold输送以及菌体-溶酶体融合.
主要成果:
- 缺乏CHM (CHM-) 细胞表现出更多的溶酶体.
- 在CHM细胞中,光受体外段 (POS) 的细胞消化受损.
- 观察到未消化的POS物质的积累,以及胞体延迟的LAMP1获取.
结论:
- 失去REP-1会导致细微的溶酶体通路功能障碍,特别影响着虫体向和消化.
- 这种损伤有助于有毒的自光材料的积累,模仿过早衰老.
- 渐进的RPE和光受体退化,导致CHM患者的视力丧失,可能是由这种渐进的溶酶体功能障碍驱动的.
更多相关视频
08:33Efficient Dissection and Culture of Primary Mouse Retinal Pigment Epithelial Cells
Published on: February 10, 2021
6.4K
10:39Author Spotlight: Improved Lipofuscin Models and Quantification of Outer Segment Phagocytosis Capacity in Highly Polarized Human Retinal Pigment Epithelial Cultures
Published on: April 14, 2023
2.7K
相关概念视频
Delivery Pathways to the Lysosome
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Lysosomal Hydrolases
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Export of Misfolded Proteins out of the ER
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
Photoreceptors and Visual Pathways
At the molecular level, visual signals trigger transformations in photopigment molecules, resulting in changes in the photoreceptor cell's membrane potential. The photon's energy level is denoted by its wavelength, with each specific wavelength of visible light associated with a distinct color. The spectral range of visible light, classified as electromagnetic radiation, spans from 380 to 720 nm. Electromagnetic radiation wavelengths exceeding 720 nm fall under the infrared category, whereas...
Diabetic Retinopathy
DefinitionDiabetic retinopathy is a microvascular complication of diabetes affecting the retinal blood vessels.Risk FactorsDiabetic retinopathy is present in almost all individuals with type 1 diabetes and more than 60% of those with type 2 diabetes after two decades of disease.The risk increases with poor glycemic control, hypertension, dyslipidemia, smoking, pregnancy, and puberty.Although cataracts and glaucoma are also more frequent in people with diabetes, retinopathy remains the leading...
