GDF11 supplementation improved retinal structure and function in retinal ischemia injury.
Adv Ophthalmol Pract Res 2026 May-Jun; 6(2):182-191.

Abstract

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.

Authors+Show Affiliations

Zhang XDepartment of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yang YDepartment of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yin JDepartment of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Peng JDepartment of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiao HDepartment of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Lu ZDepartment of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. Department of Ophthalmology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Wen YDepartment of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. Department of Ophthalmology, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Zhang WDepartment of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Liu HDepartment of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Liu MDepartment of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chen EDepartment of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wu MDepartment of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhang XDepartment of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wang MDepartment of Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Xu YDepartment of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Feng HDepartment of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhao PDepartment of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

42200087