GDF11 supplementation improved retinal structure and function in retinal ischemia injury.Adv Ophthalmol Pract Res 2026 May-Jun; 6(2):182-191.AO
Background
Retinal ischemia is a major cause of blindness and plays a detrimental role in various diseases, including occlusion of arteries or veins, diabetic retinopathy, and ocular ischemic syndrome, which could lead to the neuronal and vascular dysfunction. As a result, maintaining their activities may help to avoid visual loss. Growth differentiation factor 11 (GDF11) has been implicated that exert neuroprotective effects and promote the angiogenesis after cerebral or cardiac ischemic injury. Here, we demonstrate that GDF11 has a protective effect on ischemia retinal injury.
Methods
To simulate the morphological and functional results following retinal ischemia, a mouse unilateral common carotid artery occlusion (UCCAO) model was employed. Electroretinography (ERG) was conducted to assess the severity of retinal impairment. The effects were evaluated using hematoxylin and eosin (H&E)-staining and immunohistochemistry. In addition, angiogenic activity affected by retinal ischemia was assessed in vivo and in vitro models.
Results
We successfully established the UCCAO model and expanded the pathological understanding of UCCAO-induced retinal ischemia. The treatment with GDF11 attenuated cell death, retinal edema, gliosis and apoptosis processes in the acute phase after UCCAO. In addition, GDF11 further reduced apoptosis and improved angiogenesis in the chronic phase after UCCAO. Mechanistically, GDF11 exerted its protective effects by activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, underscoring its potential as a multifaceted therapeutic agent for retinal ischemia.
Conclusions
Our study shows the potential of GDF11 as a novel therapeutic for recovering retinal function following retinal ischemia. The results reveal that the therapeutic benefits of GDF11 are exerted during the acute and chronic phases following retinal ischemic injury.


