Abstract
Age-associated loss of retinal ganglion cells (RGCs) causes visual deficits, but there is not yet any therapeutic agent to prevent the loss of these cells. Herein, we report that apelin, an endogenous peptide ligand of APJ receptor, is protective against the age-related loss of RGCs in mice. The mRNA expression of apelin was reduced in the retina of old mice compared with that in young mice, whereas retinal APJ expression increased with age. Immunofluorescence staining showed that APJ was present in RGCs and their surrounding cells expressed apelin. In addition, both functional and histological analyses demonstrated that apelin deficiency accelerated the loss of RGCs associated with age in mice. These results suggest that endogenous apelin plays a protective role against the degeneration of RGCs and that the apelinergic axis may be a new target for preventing age-related visual impairment.
Highlights
Age-related visual impairments can occur even in the absence of recognized eye diseases (Trick, 1987; Langrová et al, 2008)
Apelin immunoreactivity was observed in cells belonging to the ganglion cell layer (GCL) and cells located in the inner part of the inner nuclear layer (INL) in the retinas of 2-months- and 12-months-old mice (Figure 1C)
In keeping with the report, apelin expression was markedly reduced in the retina of the old mice, indicating that senescence down-regulated the expression of apelin in the retina
Summary
Age-related visual impairments can occur even in the absence of recognized eye diseases (Trick, 1987; Langrová et al, 2008). Retinal ganglion cells (RGCs) are neurons that transmit visual information from the retina to the brain and are more vulnerable to age-related loss than other retinal neurons (Cavallotti et al, 2001; Neufeld and Gachie, 2003). We previously reported that apelin deficiency in mice accelerated the loss of motor neurons in amyotrophic lateral sclerosis (Kasai et al, 2011), which is an age-related neurodegenerative disease. It was reported that the deletion of apelin or APJ in mice exhibits enhanced cardiovascular, renal, and reproductive aging (Rai et al, 2017), suggesting that the apelin-APJ system has a crucial role in cell and tissue homeostasis
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