SMP30 Alleviates Oxidative Stress and Regulates Ca2+-ATPase Activity in UVR-B-Induced Cataracts in Rats.

Abstract

Purpose: Oxidative stress, ultraviolet radiation, and calcium imbalance are key components in the onset and advancement of cataract, which continue to be the leading cause of blindness globally. An important newly discovered aging maker, Senescence marker protein 30 (SMP30) regulates calcium and participates in mitigating oxidative stress damage. Here, we examined the beneficial role of SMP30 in protecting against ultraviolet radiation type B (UVR-B)-induced cataract in rats.

Methods: Wistar rats (2 months) were arbitrarily assigned into 4 groups of 10 rats. These groups included the Control group, UVR-B group, adeno-associated virus 2 vectors negative control (AAV2-NC) group, and adeno-associated virus 2-mediated overexpression of SMP30 (AAV2-SMP30) group. The control group received Phosphate-buffered saline (PBS) via injection, while the AAV2-NC group and AAV-SMP30 group were separately injected with AAV2-NC and AAV2-SMP30 vectors. In addition to the control group, the remaining three experimental groups were subjected to ultraviolet light exposure 4 weeks post-injection. The lens opacity was examined by stereoscopic microscope, and the lenses were separated to measure oxidative damage parameters particularly superoxide dismutase (SOD), glutathione peroxidase (GPX), and Ca²⁺-ATPase activity. The localization and expression of SMP30 and Ca²⁺-ATPase in the lenses were determined using immunohistochemistry and RT-qPCR.

Results: After UVR-B irradiation, the AAV2-SMP30 group exhibited a substantial decrease in lens opacity compared to the UVR-B group. The results revealed a notable downregulation of SMP30 expression and the activities of SOD, GPX, and Ca²⁺-ATPase of rat lens following exposure to UVR-B radiation. However, SMP30 overexpression partially reversed these effects. In vivo experiments demonstrated SMP30 overexpression attenuated the UVR-B-induced decline in SOD, GPX, and Ca²⁺-ATPase activities.

Conclusion: This study demonstrates that SMP30 has the potential to reduce lens opacity caused by UVR-B by increasing antioxidant stress and regulating Ca²⁺-ATPase activity. SMP30 might be a cutting-edge target for the treatment of cataracts.