Berberine Alleviates Chronic Retinal Light Damage in Mice: A Study of the Role of P2X7R and the Mechanisms Involved

Abstract

To investigate the trend of dynamic changes and the mechanisms of P2X7R by which berberine (BBR) alleviates chronic retinal light injury in mice.

Methods A total of 90 mice were randomly divided into three groups, a blank control group (n = 10), a group exposed to low-intensity blue light (500 lux) for 12 hours per day for a duration of 3 months, which was referred to as the LD group (n = 40), and another group given BBR at a dose of 200 mg/kg via gastric gavage on top of the blue light exposure for the LD group, which was referred to as the LD + BBR group (n = 40). After the light exposure and gavage were completed, eye tissues were collected from the mice. Hematoxylin and eosin (HE) staining was performed to observe the protective effects of berberine on chronic retinal light damage in mice. TUNEL assay was performed to assess the effect of berberine on apoptotic cells in mice with chronic retinal light injury. Additionally, quantitative polymerase chain reaction (QPCR) was performed to assess the expression level of P2X7 receptors in chronic retinal light injury relieved by BBR.

Results Compared with the blank control group, the LD group exhibited abnormal retinal morphology, with some ganglion cells displaying reduced nuclei, a deeper stain, and loose arrangement. In the LD group, the cells in the inner nuclear layer appeared to be slightly more loosely arranged, while the cells in the outer nuclear layer cells were arranged in a disorderly way. Furthermore, the thickness of the outer nuclear layer of the retina from mice in the LD group was (47.11 ± 2.01) μm, and a significant number of apoptotic cells were observed in the outer nuclear layer, resulting in an apoptosis rate of (71.16 ± 5.99)% (P < 0.05). In contrast, the LD + BBR group showed mild abnormal retinal morphology with loosely arranged ganglion cells. In the LD + BBR group, the cells in both inner and outer nuclear layers of retina exhibited relatively intact morphology, uniform staining pattern, and tight arrangement. Moreover, the thickness measurement for outer nuclear layer revealed a value of (54.07 ± 2.05) μm, and there were only a few apoptotic cells present, resulting in an apoptotic rate of (16.02 ± 2.68)% (P < 0.05). Compared with that of the blank control group, the relative expression of P2X7R mRNA in the retinas of the LD group was upregulated, with the difference between the two groups being statistically significant (P < 0.05). The relative expression of P2X7R mRNA in the retinas of the LD + BBR group was downregulated, showing no statistical significance compared with that of the blank control group. However, compared with that of the LD group, the relative expression of P2X7R mRNA in the retinas of the LD + BBR group showed a significant downward trend, and the difference between the two groups was statistically significant (P < 0.05).

Conclusion Berberine can alleviate chronic retinal photodamage in mice, and inhibit the activation of P2X7R, thereby preventing the formation of retinal photodamage.

Keywords: P2X7 receptors, Berberine, Retinal photodamage, Age-related macular degeneration