Unmasking inhibition prolongs neuronal function in retinal degeneration mouse model.

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.

Delay of cone degeneration in retinitis pigmentosa using a 12-month treatment with Lycium barbarum supplement.

ETHNOPHARMACOLOGICAL RELEVANCE: Lycium barbarum L. (also known as "Goji berry"), a traditional Chinese herbal medicine, has been a common herb in the traditional Chinese pharmacopoeia for centuries. The main active component is the Lycium barbarum polysaccharides and its antioxidative effect has been widely shown to provide neuroprotection to the eye, and it would, therefore, be interesting to determine if Lycium barbarum help delay vision deterioration in patients with retinitis pigmentosa. AIM OF THE STUDY: Cone rescue is a potential method for delaying deterioration of visual function in Retinitis pigmentosa (RP). This study aimed to investigate the treatment effect of Lycium barbarum L. (LB) supplement on retinal functions and structure in RP patients after a 12-month intervention trial. METHODS: The investigation was a double-masked and placebo-controlled clinical study. Each of forty-two RP subjects who completed the 12-month intervention (23 and 19 in the treatment and placebo groups respectively) received a daily supply of LB or placebo granules for oral administration. The primary outcome was change of best corrected visual acuity (VA) (90% and 10% contrast) from the baseline to the end of treatment. The secondary outcomes were sensitivity changes of the central visual field, amplitude of full-field electroretinogram (ffERG) (including scotopic maximal response and photopic cone response), and average macular thickness. RESULTS: The compliance rates for both groups exceeded 80%. There were no deteriorations of either 90% or 10% contrast VA in the LB group compared with the placebo group (p = 0.001). A thinning of macular layer was observed in the placebo group, which was not observed in the LB group (p = 0.008). However, no significant differences were found in the sensitivity of visual field or in any parameters of ffERG between the two groups. No significant adverse effects were reported in the treatment group. CONCLUSIONS: LB supplement provides a neuroprotective effect for the retina and could help delay or minimize cone degeneration in RP. CLASSIFICATIONS: Clinical Studies (1.05). TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT02244996.