Unmasking inhibition prolongs neuronal function in retinal degeneration mouse model
| Autor: | Chung Him So, Qin Wang, Dennis Y. Tse, Seema Banerjee, Feng Pan, Chun Ting Qiu, Béla Völgyi, Hang-I Christie Lam |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Retinal Ganglion Cells
0301 basic medicine Retinal degeneration Light genetic structures Central nervous system Inhibitory postsynaptic potential Biochemistry Retinal ganglion Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Retinal Rod Photoreceptor Cells Retinitis pigmentosa Genetics medicine Animals Picrotoxin Molecular Biology Vision Ocular Neurons Retina Behavior Animal business.industry Retinal Degeneration Retinal Receptors GABA-A medicine.disease eye diseases Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure chemistry Retinal Cone Photoreceptor Cells sense organs business Neuroscience Erg 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | The FASEB Journal. 34:15282-15299 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.202001315rr |
| Popis: | All neurodegenerative diseases involve a relatively long period of timeframe from the onset of the disease to complete loss of functions. Extending this timeframe, even at a reduced level of function, would improve the quality of life of patients with these devastating diseases. The retina, as the part of the central nervous system and a frequent site of many distressing neurodegenerative disease, provides an ideal model to investigate the feasibility of extending the functional timeframe through pharmacologic intervention. Retinitis Pigmentosa (RP) is a group of blinding diseases. Although the rate of progression and degree of visual loss varies, there is usually a prolonged time before patients totally lose their photoreceptors and vision. It is believed that inhibitory mechanisms are still intact and may become relatively strong after the gradual loss of photoreceptors in RP patients. Therefore, it is possible that light-evoked responses of retinal ganglion cells and visual information processes in retinal circuits could be "unmasked" by blocking these inhibitory mechanisms restoring some level of visual function. Our results indicate that if the inhibition in the inner retina was unmasked in the retina of the rd10 mouse (the well-characterized RP mimicking, clinically relevant mouse model), the light-evoked responses of many retinal ganglion cells can be induced and restore their normal light sensitivity. GABA A receptor plays a major role in this masking inhibition. ERG b-wave and behavioral tests of spatial vision partly recovered after the application of PTX. Hence, removing retinal inhibition unmasks signalling mediated by surviving cones, thereby restoring some degree of visual function. These results may offer a novel strategy to restore the visual function with the surviving cones in RP patients and other gradual and progressive neurodegenerative diseases. |
| Databáze: | OpenAIRE |
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