Neuroprotective strategies for retinal disease

Neurodegenerative diseases of the retina result from diverse insults, including genetic mutations, metabolic deficiencies, vascular compromise, and inflammatory injury. These processes converge on dysfunction of the neurovascular unit, where neurons, glia, and vascular cells cooperate to maintain retinal health. Thus, neuroprotection must be considered in a broader context that incorporates support of glial and vascular elements in addition to neurons. In this chapter, we review both classical and emerging neuroprotective strategies in retinal disease. We summarize preclinical and clinical studies of trophic factor-based approaches, including ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), fibroblast growth factor 2 (FGF2), insulin-like growth factor-1 (IGF-1), and transforming growth factor-β (TGF-β), outlining mechanisms, efficacy, limitations, and safety. We also highlight nonclassical agents such as mesencephalic astrocyte-derived neurotrophic factor (MANF) and the lipid mediator erucamide, which act through distinct pathways to modulate stress responses and neurovascular stability. Additional approaches, including stem cell-based therapies, extracellular vesicles, metabolic supplementation, and lifestyle interventions, are discussed. Finally, we emphasize the importance of human-derived models such as retinal explants and organoids to overcome translational barriers. Collectively, these studies suggest that multimodal strategies may offer meaningful neuroprotection and preserve vision in progressive retinal disease.