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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.

Background The rationale, objectives, study design and procedures for the longitudinal Andhra Pradesh Eye Disease Study are described. Design A longitudinal cohort study was carried out. Participants Participants include surviving cohort from the rural component of Andhra Pradesh Eye Disease Study. Methods During 1996–2000, Andhra Pradesh Eye Disease Survey was conducted in three rural (n = 7771) and one urban (n = 2522) areas (now called Andhra Pradesh Eye Disease Study 1). In 2009–2010, a feasibility exercise (Andhra Pradesh Eye Disease Study 2) for a longitudinal study (Andhra Pradesh Eye Disease Study 3) was undertaken in the rural clusters only, as urban clusters no longer existed. In Andhra Pradesh Eye Disease Study 3, a detailed interview will be carried out to collect data on sociodemographic factors, ocular and systemic history, risk factors, visual function, knowledge of eye diseases and barriers to accessing services. All participants will also undergo a comprehensive eye examination including photography of lens, optic disc and retina, Optic Coherence Tomography of the posterior segment, anthropometry, blood pressure and frailty measures. Main Outcome Measures Measures include estimates of the incidence of visual impairment and age-related eye disease (lens opacities, glaucoma and age-related macular degeneration) and the progression of eye disease (lens opacities and myopia) and associated risk factors. Results Of the 7771 respondents examined in rural areas in Andhra Pradesh Eye Disease Study 1, 5447 (70.1%) participants were traced in Andhra Pradesh Eye Disease Study 2. These participants will be re-examined. Conclusions Andhra Pradesh Eye Disease Study 3 will provide data on the incidence and progression of visual impairment and major eye diseases and their associated risk factors in India. The study will provide further evidence to aid planning eye care services.