Purchase this article with an account.
Hua Xu, Limei Zhang, Limin Gu, Lixia Lu, Guangping Gao, Weiye Li, Guoxu Xu, Juan Wang, Furong Gao, Jing-Ying Xu, Jun Yao, Fang Wang, Jingfa Zhang, Guo-Tong Xu; Subretinal Delivery of AAV2-Mediated Human Erythropoietin Gene Is Protective and Safe in Experimental Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2014;55(3):1519-1530. doi: https://doi.org/10.1167/iovs.13-13155.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
We studied and developed a gene-based intraocular erythropoietin (EPO) therapy for diabetic retinopathy (DR), by which the applicability of neuroprotective therapy with favorable safety profile is attempted.
Hematocrit (Hct) was measured in C57BL/6 mice after intramuscular injection of AAV2-CMV-hEPO virus. Diabetes was induced by intraperitoneal injection of streptozotocin in Sprague-Dawley (SD) rats. Subretinal or intravitreal injection was performed in SD rats and Dark Agouti (DA) rats. The human EPO (hEPO) concentration was measured with ELISA. Blood–retinal barrier (BRB) breakdown was measured with Evans blue permeation. Retinal function was evaluated with electroretinography (ERG). Retinal cell apoptosis was detected with TUNEL. Retinal thickness and cell counts were examined by light microscopy. Retinal vascular changes were evaluated with fundus fluorescein angiography (FFA) and confocal microscopy.
The serum hEPO was elevated 2 weeks after AAV2-CMV-hEPO virus injection, and Hct began to increase after 4 weeks. After subretinal injection, hEPO expressions in aqueous humor, vitreous, and retina followed a dose- and time-dependent manner. In the AAV2-CMV-hEPO–treated diabetic group, BRB was maintained, and retinal cell apoptosis was significantly reduced. The ERG results showed that the retinal function remained unchanged for at least one year after subretinal injection of AAV2-CMV-hEPO virus. Long-term expression of hEPO following subretinal injection of AAV2-CMV-hEPO virus did not induce neovascularization in retina and choroid.
The AAV2-CMV-hEPO gene therapy is safe, and it exerts long-term protective effects on diabetic retinas. Thus, the gene therapy by using AAV2-CMV-hEPO for DR is feasible.
This PDF is available to Subscribers Only