Curcumol targets the FTO/MAFG-AS1 axis to alleviate diabetic retinopathy via epigenetic remodeling and nanodelivery-based microenvironment modulation

Table 2 Cell type-specific effects within the retinal microenvironment

Cell type	Normal function	Pathological changes in DR	Interaction with other cells	Response to curcumol	Therapeutic significance
Retinal vascular endothelial cells	Maintain blood-retinal barrier, regulate vascular permeability	Abnormal proliferation, increased migration, decreased tight junction proteins	Reduced interaction with pericytes, enhanced interaction with microglia	Inhibits proliferation and migration, restores tight junction protein expression	Primary therapeutic target; improves vascular function, reduces leakage
Pericytes	Maintain capillary stability, regulate blood flow	Reduced number, impaired function, decreased contact with endothelial cells	Disrupted communication with endothelial cells, causing vascular instability	Improves pericyte-endothelial interaction, stabilizes microvascular structure	Protective therapeutic target; preventing pericyte loss is critical
Microglia	Immune surveillance, neuroprotection, synaptic pruning	Increased activation, morphological changes, elevated Iba-1 expression	Release inflammatory cytokines affecting endothelial cells and neurons	Suppresses activation, reduces neuroinflammation, protects neuronal function	Emerging therapeutic target; modulates neuroinflammation
Müller glial cells	Structural support, ion homeostasis, metabolic support	Activation, increased GFAP expression, release of VEGF and inflammatory cytokines	Metabolic support for all retinal cell types	Attenuates glial activation, reduces VEGF expression	Important regulatory target; maintains overall retinal homeostasis
Retinal ganglion cells	Visual signal transmission, visual information integration	Dysfunction, axonal degeneration, increased apoptosis	Affected by microglial inflammation and Müller cell dysfunction	Reduces oxidative stress damage, protects neuronal survival	Neuroprotective target; prevents irreversible vision loss
Retinal pigment epithelium	Outer blood-retinal barrier, supports photoreceptors	Barrier impairment, pigmentary changes, lipid deposition	Interacts with photoreceptors and choroidal vessels	Enhances antioxidant capacity, maintains epithelial integrity	Adjunct therapeutic target; preserves overall retinal function

DR: Diabetic retinopathy; GFAP: Glial fibrillary acidic protein; Iba-1: Ionized calcium-binding adapter molecule 1; VEGF: Vascular endothelial growth factor.