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Updated: Jun 11, 2025
Mouse Eye Enucleation for Remote High-throughput Phenotyping
Published on: November 19, 2011
Deletion of Transmembrane protein 184b leads to retina degeneration in mice
Guo Liu1,2, Tiannan Liu1, Junkai Tan3
1The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Center for Medical Genetics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Abstract:
Transmembrane protein 184b (Tmem184b) has been implicated in axon degeneration and neuromuscular junction dysfunction. Notably, Tmem184b exhibits high expression levels in the retina; however, its specific function within this tissue remains poorly understood. To elucidate the role of Tmem184b in the mammalian visual system, we developed a Tmem184b knockout (KO) model for further investigation. Loss of Tmem184b led to significant decreases in both a and b wave amplitudes of scotopic electroretinogram (ERG) and reduced b wave amplitudes of photopic ERG, respectively, reflecting damage to both the photoreceptors and secondary neuronal cells of the retina. Histologic analyses showed a progressive retinal thinning accompanied by the significantly loss of retinal cells including cone, rod, bipolar, horizontal and retinal ganglion cells. The expression levels of photo-transduction-related proteins were down-regulated in KO retina. TUNEL (terminal deoxynucleotidyl transferase-mediated biotinylated Uridine-5'-triphosphate [UTP] nick end labelling) and glial fibrillary acidic protein (GFAP)-labelling results suggested the increased cell death and inflammation in the KO mice. RNA-sequencing analysis and GO enrichment analysis revealed that Tmem184b deletion resulted in down-regulated genes involved in various biological processes such as visual perception, response to hypoxia, regulation of transmembrane transporter activity. Taken together, our study revealed essential roles of Tmem184b in the mammalian retina and confirmed the underlying mechanisms including cell death, inflammation and hypoxia pathway in the absence of Tmem184b, providing a potential target for therapeutic and diagnostic development.
Insights
Transmembrane protein 184b (Tmem184b) is crucial for retinal health, preventing cell death and inflammation. Its absence causes significant visual system damage, impacting photoreceptors and neuronal cells.
Area of Science:
- Neuroscience
- Ophthalmology
- Cell Biology
Background:
- Transmembrane protein 184b (Tmem184b) is linked to axon degeneration but its retinal function is unknown.
- Tmem184b is highly expressed in the retina, suggesting a key role in visual function.
Purpose of the Study:
- To investigate the function of Tmem184b in the mammalian retina.
- To elucidate the molecular mechanisms underlying retinal dysfunction in Tmem184b-deficient mice.
Main Methods:
- Developed a Tmem184b knockout (KO) mouse model.
- Performed electroretinography (ERG), histologic analysis, TUNEL and GFAP staining, and RNA-sequencing.
Main Results:
- Tmem184b KO mice showed reduced ERG amplitudes, progressive retinal thinning, and loss of various retinal cells.
- Down-regulation of phototransduction proteins, increased cell death, inflammation, and altered gene expression related to visual perception and hypoxia were observed.
- Tmem184b deletion impacted genes involved in visual perception, hypoxia response, and transmembrane transport.
Conclusions:
- Tmem184b plays essential roles in maintaining retinal structure and function.
- Mechanisms include regulation of cell death, inflammation, and hypoxia pathways.
- Tmem184b presents a potential therapeutic target for retinal diseases.
