Elucidating programmed cell death in diabetic retinal microangionopathy and neurodegeneration: unraveling molecular mechanisms and therapeutic actions of natural products

Diabetic retinopathy (DR) is a common diabetes condition that contributes significantly to vision impairment and blindness in working-age people. The classical theory contends that DR is solely a retinal microvascular disorder. Nevertheless, a growing body of research has demonstrated that the pathological variations of DR consist of retinal microangiopathy and retinal neurodegeneration triggered by hyperglycemia. When these two pathological alterations arise, they are commonly accompanied by programmed cell death (PCD) in the retina. With the intensification of research on retinal pathology, PCD has emerged as a matter of concern in the study of DR. Programmed cell death includes apoptosis, pyroptosis, autophagy and ferroptosis. These four approaches can deal with DR by mediating the death of blood vessels and nerve cells to preserve the homeostasis of the internal environment within the retina. Notably, numerous natural products have been demonstrated to influence PCD, resulting in vascular and neuroprotective effects. This study offers a thorough analysis of the molecular processes that underlie different types of PCDs and clarifies how they affect the development of neurodegeneration and retinal microangiopathy. Additionally, this review systematically outlines the regulatory effects of natural products on PCD, highlighting their potential mechanisms and clinical applications in two pathological stages of treatment. This targeted approach not only enhances the relevance of this paper in the study of diabetic retinal microangiopathy and neurodegeneration but also provides new insights into the development of drug treatments for different stages of DR.