Abstract
Age and gender are two important factors that may influence the function and structure of the retina and its susceptibility to retinal diseases. The aim of this study was to delineate the influence that biological sex and age exert on the retinal structural and ultrastructural changes in mice and to identify the age-related miRNA dysregulation profiles in the retina by gender. Experiments were undertaken on male and female Balb/c aged 24 months (approximately 75–85 years in humans) compared to the control (3 months). The retinas were analyzed by histology, transmission electron microscopy, and age-related miRNA expression profile analysis. Retinas of both sexes showed a steady decline in retinal thickness as follows: photoreceptor (PS) and outer layers (p < 0.01 for the aged male vs. control; p < 0.05 for the aged female vs. control); the inner retinal layers were significantly affected by the aging process in the males (p < 0.01) but not in the aged females. Electron microscopy revealed more abnormalities which involve the retinal pigment epithelium (RPE) and Bruch’s membrane, outer and inner layers, vascular changes, deposits of amorphous materials, and accumulation of lipids or lipofuscins. Age-related miRNAs, miR-27a-3p (p < 0.01), miR-27b-3p (p < 0.05), and miR-20a-5p (p < 0.05) were significantly up-regulated in aged male mice compared to the controls, whereas miR-20b-5p was significantly down-regulated in aged male (p < 0.05) and female mice (p < 0.05) compared to the respective controls. miR-27a-3p (5.00 fold; p < 0.01) and miR-27b (7.58 fold; p < 0.01) were significantly up-regulated in aged male mice vs. aged female mice, whereas miR-20b-5p (−2.10 fold; p < 0.05) was significantly down-regulated in aged male mice vs. aged female mice. Interestingly, miR-27a-3p, miR-27b-3p, miR-20a-5p, and miR-20b-5p expressions significantly correlated with the thickness of the retinal PS layer (p < 0.01), retinal outer layers (p < 0.01), and Bruch’s membrane (p < 0.01). Our results showed that biological sex can influence the structure and function of the retina upon aging, suggesting that this difference may be underlined by the dysregulation of age-related mi-RNAs.
Highlights
The structural and functional physiological evolution of the retina with age can be influenced by biological sex and susceptibility to retinal diseases (Wagner et al, 2008; Freund et al, 2011)
The retinal pigment epithelium (RPE) and retinal ganglion cell layer (GGL) reduced approximately onefold in older mice compared to young ones and were similar for both sexes
Other results did not show a significant difference between the thickness of the retinal layers and age, by sex in groups of Sprague Dawley rats aged 1, 2, 6, and 10 months (Chaychi et al, 2015), which highlights that major structural changes appear only in the second year of life in rodents
Summary
The structural and functional physiological evolution of the retina with age can be influenced by biological sex and susceptibility to retinal diseases (Wagner et al, 2008; Freund et al, 2011). There are anatomical sex differences, visual performances, and divergent molecular profiles (Du et al, 2017) by gender upon aging, which may contribute to different susceptibilities to disease and trace different evolutions for retinal pathologies (Wagner et al, 2008; Ozawa et al, 2015; Schmidl et al, 2015). Clinical results have reported that women have thinner retinas than men, without any differences in the foveal pit morphology (Wagner-Schuman et al, 2011), whereas the amplitudes of scotopic and photopic electroretinograms (ERGs) of female subjects have been reported to be on average 29% larger than those of males (Brulé et al, 2007). The outer nuclear layers and the inner nuclear layer (INL) have been determined to be thicker in men, whereas the nerve fiber layer (NFL) is thicker in women (Ooto et al, 2011)
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