Role of endoplasmic reticulum stress in the loss of RGCs in diabetic retinopathy

Endoplasmic reticulum stress is closely involved in the early stage of diabetic retinopathy. According a study published in the Neural Regeneration Research (Vol. 8, No. 33, 2013), endoplasmic reticulum stress played an important role in the hyperglycemia-induced death of ganglion cells and impairment of retinal microvessels.

Tauroursodeoxycholic acid treatment effectively inhibited the activation of the endoplasmic reticulum stress pathway, and provided effective protection against diabetic retinopathy. The C/ERB homologous protein was shown to co-localize with glial fibrillary acidic protein-positive glial cells in the retina of diabetic rats, and subsequently provided evidence for the activation of glial cells in diabetic retinopathy.

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Article: " Role of endoplasmic reticulum stress in the loss of retinal ganglion cells in diabetic retinopathy," by Liping Yang1, Lemeng Wu1, Dongmei Wang1, Ying Li1, Hongliang Dou1, Mark O.M.Tso1, 2, Zhizhong Ma1 (1 Department of Ophthalmology, Peking University Third Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing 100191, China; 2 Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA)

Yang LP, Wu LM, Wang DM, Li Y, Dou HL,Tso MO, Ma ZZ. Role of endoplasmic reticulum stress in the loss of retinal ganglion cells in diabetic retinopathy. Neural Regen Res. 2013;8(33):3148-3158.

Role of endoplasmic reticulum stress in the loss of retinal ganglion cells in diabetic retinopathy

Abstract
Endoplasmic reticulum stress is closely involved in the early stage of diabetic retinopathy. In the present study, a streptozotocin-induced diabetic animal model was given an intraperitoneal injection of tauroursodeoxycholic acid. Results from immunofluorescent co-localization experiments showed that both caspase-12 protein and c-Jun N-terminal kinase 1 phosphorylation levels significantly increased, which was associated with retinal ganglion cell death in diabetic retinas. The C/ERB homologous protein pathway directly contributed to glial reactivity, and was subsequently responsible for neuronal loss and vascular abnormalities in diabetic retinopathy. Our experimental findings indicate that endoplasmic reticulum stress plays an important role in diabetes-induced retinal neuronal loss and vascular abnormalities, and that inhibiting the activation of the endoplasmic reticulum stress pathway provides effective protection against diabetic retinopathy.

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Diabetic retinopathy is one of the most common complications associated with diabetes mellitus and the leading cause of blindness in adults. Mechanisms underlying diabetic retinopathy onset and progression are not fully elucidated. Both neuronal and vascular abnormalities are associated with the pathogenesis of early diabetic retinopathy. The death of neurons is irreversible and directly affects visual function. The most severely affected neurons in diabetic retinopathy are retinal ganglion cells. Therefore, understanding the etiology of neuronal loss and vascular abnormalities will lead to better treatments for diabetic retinopathy.