AIM:To investigate the mechanism by which Shuangdan Mingmu Capsules alleviate retinal inflammatory responses in mice with diabetic retinopathy(DR)through the inhibition of the cGAS-STING signaling pathway.

METHODS:SPF C57BL/6J male mice were first randomly divided into two groups: a DR model group(n=30)receiving daily intraperitoneal STZ injections(50 mg/kg)for 5 d, and a normal control group(n=10)receiving equivalent sodium citrate buffer. After successful diabetes induction, the mice were randomly divided into model group, Shuangdan Mingmu Capsules group, and positive drug group, with 10 mice in each group. The Shuangdan Mingmu Capsules group received gavage with Shuangdan Mingmu Capsules solution at a clinically equivalent dose(11.2 g/kg), while the positive drug group received gavage with Calcium Dobesilate solution at an equivalent dose of 11.6 mg/kg. The model group and the normal group received gavage with an equal volume of normal saline. Each group of mice received gavage once daily, and after 8 weeks of intervention treatment, Evans blue staining was used to detect the retinal leakage in each group of mice, HE staining was used to detect changes in the retinal tissue structure, TUNEL staining was used to observe the apoptosis of retinal cells, and immunofluorescence was used to detect the expression levels of retinal Rhodopsin, Opsin, Iba1 and GFAP. Furthermore, Western blot was used to detect the protein expression levels of cGAS, STING, TNF-α, IL-6 and IL-1β in the mouse retina.

RESULTS:Compared with the normal group, the model group mice exhibited increased levels of neuroretinal leakage, retinal thinning, and elevated retinal cells apoptosis, accompanied by upregulation of Iba1 and GFAP expression levels in the retina, and downregulation of Rhodopsin and Opsin expression. The protein expression levels of cGAS, STING, TNF-α, IL-6, and IL-1β in the retinal tissue were significantly increased. In contrast to the model group, the Shuangdan Mingmu Capsules group and positive drug group mice showed decreased levels of neuroretinal leakage and retinal cells apoptosis, along with downregulation of Iba1 and GFAP expression levels in the retina, and upregulation of Rhodopsin and Opsin expression. The protein expression levels of cGAS, STING, TNF-α, IL-6, and IL-1β in the retinal tissue were significantly decreased. However, there was no significant difference between the Shuangdan Mingmu Capsules group and the positive drug group.

CONCLUSION:Shuangdan Mingmu Capsules exert therapeutic effects on retinal inflammation and early damage in DR mouse models, with the underlying mechanism involving the inhibition of the cGAS-STING signaling pathway.