VEGF-A/VEGFR2 expression in RHO-P23H mice: effects of BDNF intravitreal injections.

Vascular endothelial growth factor A (VEGF-A) plays a crucial role in retinal homeostasis and pathology, with its activity finely regulated by the balance between pro- and anti-angiogenic isoforms and by signaling through its main receptor, VEGFR2. Dysregulation of this system has been implicated in retinal degenerative diseases. Brain-derived neurotrophic factor (BDNF) exerts neuroprotective effects in the retina; however, its interaction with the VEGF-A/VEGFR2 pathway remains poorly understood. This study aimed to evaluate changes in the expression of VEGF-A, its major isoforms, and VEGFR2 in the retina of the RHO-P23H mouse model of retinal degeneration, and to assess the effects of intravitreal BDNF administration. RHO-P23H mice received a single intravitreal BDNF injection at postnatal day 18, and retinas were analyzed at two months of age. Total VEGF-A, including VEGF-A165, VEGF-A121, and VEGF-A189, was elevated in vehicle-treated RHO-P23H mice compared to wild-type controls and further increased following BDNF, suggesting crosstalk between VEGF-A and BDNF pathways. Anti-angiogenic VEGF-Axxxb isoforms showed a marked reduction of VEGF-A165b in diseased retinas, partially restored by BDNF, while the treatment strongly modulated VEGF-A121b. VEGFR2 was downregulated in the degenerative model but markedly upregulated after BDNF administration. Overall, these findings highlight the critical role of VEGF-A regulation in retinal degeneration, with particular emphasis on anti-angiogenic isoforms. The observed modulation of VEGF-Axxxb underscores its dual role in maintaining angiogenic balance and promoting retinal neuroprotection, while revealing important cross-talk with neurotrophins, providing new insights into the mechanisms underlying retinal degenerative diseases.