Subarachnoid Hemorrhage Reduces Retinal Ganglion Cells, Increases New Vessel Development

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Using animal models, researchers determine subarachnoid hemorrhage can lead to new vessel development and the reduction of ganglion cells.

Subarachnoid hemorrhage and associated retinal hypoxia can result in a reduction of retinal ganglion cells, cause the development of retinal new vessels, and activate hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF)-A pathways. This is according to research results published in Neuroscience Letters. 

In an experimental animal model study, researchers set out to evaluate retina morphology after subarachnoid hemorrhage, since no reports on these pathological changes currently exist. Rats were divided into 9 groups; each was anesthetized and injected with 0.3 mL nonheparinized, fresh, autologous arterial blood in the subarachnoid space. After being euthanized, retinal tissues were separated, collected, and evaluated. 

An immunofluorescence analysis indicated the presence of “significantly fewer” Brn-3a+ cells in the inner retina 1 day after subarachnoid hemorrhage, compared with the control group. Hematoxylin and eosin staining experiments demonstrated retinal new vessels in retinal ganglion cells later, and an intact endothelial structure; growing into the vitreous cavity was also observed at 12 and 24 hours post-subarachnoid hemorrhage. 

Immunofluorescence and immunohistochemical staining of CD31 indicated “extensive” retinal new vessels in the retinal ganglion cell layer compared with rats in the control group. These newly formed retinal new vessels, the researchers noted, grew through the surface of the retina and into the vitreous. 

Expression levels of HIF-1α and CD31 were measured to detect potential retinal hypoxia. Double immunofluorescence analysis demonstrated substantial colocalization of both HIF-1α and CD31 in the retinal ganglion cell layer. Grey values of 3 different fluorescence channels were measured, with results indicating highly consistent fluorescence distribution in each channel. Similarly, immunochemical staining indicated much higher HIF-1α expression in the retinal ganglion cell layer, compared with the control group. 

Study results, the research concludes, show that subarachnoid hemorrhage “induced the retina hypoxia resulting in the reduction of [retinal ganglion cells], increase of [retinal new vessels], and activations of [retinal new vessels]-related HIF-1α/VEGF-A pathway.” 


Zhaba W-D, Deji Q-Z, Deng H-J, et al. Retinal hypoxia after experimental subarachnoid hemorrhage. Neurosci Lett. Published online December 19, 2020. doi:10.1016/j.neulet.2020.135554