Purpose: Apoptosis is a key process in neural degeneration associated with retinal vascular diseases. Vascular endothelial growth factor (VEGF) antagonists, including bevacizumab, are used to treat macular edema in these diseases. As VEGF has a critical role in the preservation of retinal neuronal cells, this study investigates the effects of bevacizumab on neural damage in a pig model of branch retinal vein occlusion (BRVO) and compares it with triamcinolone acetonide (TA) which is reported to possess neuroprotective properties.
Methods: Thirty-six pigs had a photothrombotic BRVO in both eyes. Six pigs were injected with bevacizumab in one eye and TA in the fellow eye, then they were sacrificed, the eyes enucleated, and retinas processed at 2, 6, 10, and 20 days, respectively, together with three pigs (six eyes) BRVO only and three normal pigs (six eyes). Neuronal degeneration (apoptosis) and associated inner retinal changes were determined by terminal deoxyynuclotidyl transferase dUTP nick-end labeling (TUNEL), histology, and immunohistochemistry for macrophages.
Results: TUNEL labeling showed significantly higher apoptosis rates in the ganglion cell layer (GCL) and the inner nuclear layer (INL) in the bevacizumab-treated compared with the TA-treated retinas at 2, 10, and 20 day time points after occlusion (P < 0.05). Pyknotic cells were significantly higher in the GCL in bevacizumab-treated eyes at 6, 10, and 20 days and in the INL at 2 days compared to TA-treated retinas (P < 0.05). Macrophage infiltration was seen at all time points in both untreated and treated retinas with an absence of significance between bevacizumab- and TA-treated retinas (P > 0.05).
Conclusions: Neurodegeneration in the BRVO acute phase is exacerbated by current standard treatments for BRVO. These results may have implications for the timing and treatment type.
Translational relevance: In the acute phase of BRVO, VEGF suppression with bevacizumab and to a lesser extent with triamcinolone exacerbates apoptosis in the inner retinal layers, which has implications for both the timing and choice of treatment.