The Neurovascular Unit in Diabetic Retinopathy: The Emerging Role of Pyroptosis and Therapeutic Prospects

Diabetic retinopathy (DR) is recognized as a neurovascular disorder, characterized by both functional impairment and structural disruption of the neurovascular unit (NVU), the functional unit of the retina. This review concentrates on the emerging role of pyroptosis, a lytic form of programmed cell death (PCD), within the NVU. We systematically discuss how pyroptosis manifests in the major cell types constituting the NVU, including neurons, Müller cells, microglia, astrocytes, endothelial cells, and pericytes, and delineate the underlying molecular pathways. Furthermore, we integrate recent and emerging evidence associated with pyroptosis and the broader concept of PANoptosis, emphasizing that future diagnostic and therapeutic strategies should transcend a single-pathway perspective to provide optimal protection for the NVU. By integrating recent advances in molecular and cellular research, this review aims to provide novel insights into preserving NVU integrity and developing targeted interventions to delay or halt the progression of DR.