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Sulforaphane delays diabetes-induced retinal photoreceptor cell degeneration
Jinjuan Lv1, Shuyin Bao2, Tianhe Liu1
1Department of Histology and Embryology, College of basic medicine, Dalian Medical University, Dalian, 116044, Liaoning Province, China.
Abstract:
Diabetic retinopathy (DR) is a serious neurodegenerative disease that is induced by hyperglycaemia. Oxidative stress, inflammation and endoplasmic reticulum (ER) stress are involved in the development of DR. Sulforaphane (SF) is widely found in cruciferous plants and has a protective effect against retinal neurodegeneration in diabetes, but the mechanism is unclear. In this study, we investigated the mechanism by which SF protects against photoreceptor degeneration in diabetes. In vivo, a mouse model of diabetes was established by streptozotocin (STZ) injection, and the mice were treated with/without SF. Electroretinography (ERG) and H&E staining were used to evaluate retinal function and morphology. In vitro, 661w cells were treated with AGEs with/without SF. Cell viability and apoptosis were analysed by CCK-8 assay and flow cytometry. The expression of proteins and genes was assessed by western blot and qRT-PCR. The amplitude of the a-wave was decreased and the morphology was changed in the diabetic mice, and these changes were delayed by SF treatment. The percentage of apoptotic cells was increased and the cell viability was decreased after the treatment of 661w cells with AGEs. Moreover, the expression of GRP78, Txnip and TNFα was increased, however, this increased expression was reversed by SF treatment via AMPK pathway activation. Taken together, these data show that SF can delay photoreceptor degeneration in diabetes, and the underlying mechanism is related to the inhibition of ER stress, inflammation and Txnip expression through the activation of the AMPK pathway.
Insights
Sulforaphane (SF) delays photoreceptor degeneration in diabetic retinopathy by inhibiting endoplasmic reticulum stress and inflammation. This protection is mediated through the activation of the AMPK pathway.
Area of Science:
- Ophthalmology
- Neuroscience
- Molecular Biology
Background:
- Diabetic retinopathy (DR) is a neurodegenerative complication of diabetes, driven by hyperglycemia.
- Oxidative stress, inflammation, and endoplasmic reticulum (ER) stress are key contributors to DR pathogenesis.
- Sulforaphane (SF), a compound from cruciferous plants, shows potential in preventing retinal neurodegeneration, but its mechanism in DR is not fully understood.
Observation:
- Diabetic mice exhibited decreased a-wave amplitude and altered retinal morphology, indicative of photoreceptor dysfunction.
- In vitro studies showed that advanced glycation end products (AGEs) increased 661w cell apoptosis and decreased viability.
- AGEs treatment elevated the expression of ER stress markers (GRP78), inflammation (TNFα), and Txnip.
Findings:
- SF treatment delayed the functional and morphological decline of photoreceptors in diabetic mice.
- SF reversed AGEs-induced apoptosis and restored cell viability in 661w cells.
- SF inhibited the expression of GRP78, Txnip, and TNFα by activating the AMP-activated protein kinase (AMPK) pathway.
Implications:
- SF demonstrates a therapeutic potential for mitigating diabetic retinopathy progression.
- Targeting ER stress, inflammation, and Txnip via the AMPK pathway presents a novel therapeutic strategy for DR.
- Understanding SF's mechanism provides insights into managing diabetes-induced retinal neurodegeneration.
