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Current therapeutic strategies rely on intraocular delivery of VEGF\u2010antagonizing reagents, which results in sustained suppression of pathogenic vascularization. Although significant advancement has been achieved in VEGF antagonism, substantial adverse effects have been reported in retrospective clinical studies. To study mechanisms for VEGF antagonism\u2010associated adverse effects in visual system, we intravitreally delivered recombinant adeno\u2010associated virusmediated expression of soluble Fms\u2010related tyrosine kinase\u20101 (rAAV.sFLT\u20101), the extracellular domain of VEGF receptor, and analyzed the morphology and functions of retinal tissue. Here, we confirmed that intraocular VEGF antagonism induced retinal degeneration and gliosis. The functional deficit in retinal response to visual stimulation was also demonstrated in rAAV.sFLT\u20101\u2010treated eyes by electroretinogram. Moreover, high\u2010throughput RNA sequencing analysis suggests that VEGF antagonism activates retinal degeneration, inflammation, and other adverse effects. Taken together, our findings have shed light on pathogenic mechanisms for VEGF antagonism\u2010associated adverse effects and potential therapeutic targets.\u2014Xiao, M., Liu, Y., Wang L., Liang, J., Wang T., Zhai, Y., Wang Y., Liu S. Liu W. Luo X. Wang F. Sun X. Intraocular VEGF deprivation induces degeneration and fibrogenic response in retina. 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