Abstract
Age-associated macular degeneration (AMD), which leads to loss of vision at its end stage, is one of the most common neurodegenerative diseases among the elderly. However, to date, no effective drug therapy is available for the prevention of AMD. Here, we report the occurrence of AMD pathology and its prevention by chronic treatment with the neurotrophic peptidergic compound P021, in aged rats and 3xTg-AD mice. We found photoreceptor degeneration, lipofuscin granules, vacuoles, and atrophy in retinal pigment epithelium (RPE) as well as Bruch’s membrane (BM) thickening; in aged rats, we even found rosette-like structure formation. Microgliosis and astrogliosis were observed in different retinal layers. In addition, we also found that total tau, phosphorylated tau, Aβ/APP, and VEGF were widely distributed in the sub-retina of aged rats and 3xTg mice. Importantly, chronic treatment with P021 for 3 months in rats and for 18 months in 3xTg mice ameliorated the pathological changes above. These findings indicate the therapeutic potential of P021 for prevention and treatment of AMD and retinal changes associated with aging and Alzheimer’s disease.
Highlights
Age-associated macular degeneration (AMD) involves the degeneration of the small central area of the retina, called macula, that controls visual acuity
When we previously evaluated the effect of chronic oral treatment with P021 on tau pathology and cognitive impairment in aged rats and mice, we did not observe any worsening in general physical state because of P021 treatment, suggesting a probable lack of any side effects (Kazim et al, 2014)
The rows and thickness of inner nuclear layer (INL) in the peripheral retina were decreased in the ∼22- to 24-month-old/Veh rats compared with the ∼5- to 6-monthold/Veh rats, and ∼22- to 24- month-old/P021 rats showed a clear trend to rescue the number of rows (Figures 1C,E,G)
Summary
Age-associated macular degeneration (AMD) involves the degeneration of the small central area of the retina, called macula, that controls visual acuity. AMD is a leading cause of vision loss in the elderly. In AMD, the macula is irreversibly destroyed, which leads to loss of vision required for activities such as driving, recognizing faces, reading, and seeing in color (Lambert et al, 2016). The prevalence of AMD increases with age. The risk of getting AMD increases from 2% at 50–59 years of age to almost 30% at 75 years of age. The number of AMD cases is estimated to reach 196 million worldwide by 2020 and 288 million by 2040 if no effective treatment is developed (Wong et al, 2014)
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