Sex and Age-Related Differences in Neuroinflammation and Apoptosis in Balb/c Mice Retina Involve Resolvin D1.

(1) Background: The pro-resolving lipid mediator Resolvin D1 (RvD1) has already shown protective effects in animal models of diabetic retinopathy. This study aimed to investigate the retinal levels of RvD1 in aged (24 months) and younger (3 months) Balb/c mice, along with the activation of macro- and microglia, apoptosis, and neuroinflammation. (2) Methods: Retinas from male and female mice were used for immunohistochemistry, immunofluorescence, transmission electron microscopy, Western blotting, and enzyme-linked immunosorbent assays. (3) Results: Endogenous retinal levels of RvD1 were reduced in aged mice. While RvD1 levels were similar in younger males and females, they were markedly decreased in aged males but less reduced in aged females. Both aged males and females showed a significant increase in retinal microglia activation compared to younger mice, with a more marked reactivity in aged males than in aged females. The same trend was shown by astrocyte activation, neuroinflammation, apoptosis, and nitrosative stress, in line with the microglia and Müller cell hypertrophy evidenced in aged retinas by electron microscopy. (4) Conclusions: Aged mice had sex-related differences in neuroinflammation and apoptosis and low retinal levels of endogenous RvD1.

Corrigendum: Changes in Retinal Structure and Ultrastructure in the Aged Mice Correlate with Differences in the Expression of Selected Retinal miRNAs.

[This corrects the article DOI: 10.3389/fphar.2020.593514.].

A novel experimental approach to evaluate guided bone regeneration (GBR) in the rat femur using a 3D-printed CAD/CAM zirconia space-maintaining barrier.

INTRODUCTION: Obtaining a certain bone volume is an important goal in implantology or orthopedics. Thus, after tooth extraction, quite a lot of horizontal and vertical alveolar bone is lost in time and can be detrimental to the implant treatment outcome, while the treatment of critical bone defects is a considerable challenge for surgery. OBJECTIVES: In this study we designed a new in vivo model as an useful experimental tool to assess guided bone regeneration (GBR) using a computer-aided design/manufacturing (CAD-CAM) space-maintaining barrier. METHODS: The barrier was 3D printed with three progressive heights, surgically placed on rat femur, and GBR results were analyzed at 2, 4, and 8 weeks by X-ray and bone mineral density analysis, histology/morphometry and by immunofluorescence and immunohistochemistry for osteogenesis and angiogenesis evaluation. RESULTS: The obtained results show that the proposed experimental model provides a real-time useful information on progressive bone tissue formation, which depends on the volume of isolated space created for GBR and on molecular events that lead to satisfactory vertical and horizontal bone augmentation and osteointegration. CONCLUSION: In conclusion, the proposed customized three-dome space-maintaining barrier is suitable as an experimental tool to assess the potential of using the designed barriers in dentistry and orthopedics to promote the formation of new bone and determine their space- and time-dependent limitations. Meanwhile, guided bone augmentation for dentistry requires subsequent evaluation on an alveolar bone preclinical model followed by clinical implementation.

Changes in Retinal Structure and Ultrastructure in the Aged Mice Correlate With Differences in the Expression of Selected Retinal miRNAs.

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.