Targeting neurotrophic dysregulation in diabetic retinopathy: a novel therapeutic avenue

The gradual retinal damage caused by chronic hyperglycemia is known as Diabetic retinopathy (DR), and it is the main cause of visual impairment and blindness in adults. The importance of neurotrophic factors in DR pathogenesis has been emphasized by recent studies. In diabetes, several naturally occurring proteins undergo substantial changes that impact neuronal survival, development, and differentiation. A number of neurotrophic factors, such as Brain-derived neurotrophic factor (BDNF), Nerve growth factor (NGF), Ciliary neurotrophic factor (CNTF), Glial cell line-derived neurotrophic factor (GDNF), Insulin-like Growth Factor-1 (IGF-1), fibroblast growth factor (FGF) play interdependent roles in DR, and this review offers a new prospective into these relationships. The processes for downregulating these neurotrophic factors were investigated, together with their altered expression patterns, action mechanisms, and therapeutic target potential, in this review. The crosstalk between neurotrophic factors and inflammatory pathways, oxidative stress, and vascular dysfunction in the diabetic retina is elucidated, offering insights into the complex neurovascular interplay in DR. Furthermore, emerging therapeutic strategies aimed at modulating neurotrophic factors to prevent or ameliorate retinal neurodegeneration are discussed. This comprehensive overview underscores the necessity for integrated approaches targeting neurotrophic support to develop effective interventions for diabetic retinopathy.