Neurotrophin–VEGF Crosstalk Regulating Ocular Homeostasis in Retinal Degeneration Models

Retinal degeneration is characterized by progressive neuronal loss, vascular dysfunction, and chronic neuro-inflammation, leading to an impairment of ocular homeostasis. Increasing evidence suggests that neurotrophins, such as Nerve Growth Factor (NGF) and Brain derived Neurotrophic Factor (BDNF), involved in survival and growth of neuronal and no neuronal cell types, and vascular endothelial growth factor (VEGF), which mediates blood vessel growth in healthy and pathological tissues, can cooperate to regulate ocular homeostasis by forming a retinal neuro-vascular unit (RNVU). The RNVU enables the integration of spatial and functional coupling between neural activity, metabolic support, and blood supply. This organization is essential for the regulation of synaptic transmission, metabolic exchange, and preservation of the inner blood–retinal barrier. In fact, when the RNVU component integrity is disrupted as per neurotrophins/VEGF disequilibrium, the retinal milieu results in local inflammation or apoptosis, impaired synaptic communication, and progressive neurodegeneration. To investigate the pathophysiology of retinal degenerative diseases related to these events, several in vitro, ex vivo and in vivo animal models have been proposed. Further, these models are currently used for studying emerging therapeutic strategies, such as those based on anti-VEGF antibodies administration and/or treatments with NGF and BDNF to counteract the progression of retinal neurodegeneration, by means of VEGF interaction and inflammation modulation.