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Title: Unmasking inhibition prolongs neuronal function in retinal degeneration mouse model
Authors: Wang Q. 
Banerjee S. 
So C. 
Qiu C. 
Lam H.-I.C. 
Tse, D 
Völgyi, B
Pan, F 
Issue Date: Nov-2020
Source: FASEB journal, Nov. 2020, v. 34, no. 11, p. 15282-15299
Abstract: 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.
Keywords: Ganglion cell
Inhibition
Neurodegenerative disease
Retina
Vision
Publisher: Federation of American Societies for Experimental Biology
Journal: FASEB journal 
ISSN: 0892-6638
EISSN: 1530-6860
DOI: 10.1096/fj.202001315RR
Rights: © 2020 Federation of American Societies for Experimental Biology
This is the peer reviewed version of the following article: Wang, Q, Banerjee, S, So, C, et al. Unmasking inhibition prolongs neuronal function in retinal degeneration mouse model. The FASEB Journal. 2020; 34: 15282– 15299, which has been published in final form at https://dx.doi.org/10.1096/fj.202001315RR. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
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