Abstract
Purpose :
To identify the effects of Adeno Associated Virus (AAV)-superoxide dismutase 3 (SOD3) on diabetes mellitus (DM)-induced retinal changes in a diabetic rat model.
Methods :
Diabetic models were established by a single tail vein injection of streptozotocin (STZ) in Sprague-Dawley rats. Intravitreal injection of AAV-SOD3 was performed before (prevetion group) STZ injection, and 3 days and 4 weeks (treatment group) following STZ injection. Scotopic and photopic electroretinography (ERG) were recorded. Immunofluorescence staining with alpha-smooth muscle actin, glial fibrillary acidic protein (GFAP), parvablumin, extracellular superoxide dismutase 3 (SOD3), 8-Hydroxy-2’deoxyguanosine (8-OHdG), Flt1 and tumor necrosis factor-alpha were evaluated. Histologic evaluation is six-micrometer-thick sections were stained with hematoxylin and eosin (H&E).
Results :
In the scotopic ERG, the diabetic group showed reduced a- and b-wave amplitudes compared with the control group. In the photopic ERG, b-wave amplitude showed significant (p < 0.0005) reduction at 32 weeks following DM induction. However, the trend of a- and b-wave reduction was not evident in the AAV-SOD3 treated group. GFAP, Flt1, parvablumin, 8-OHdG and TNF-alpha immunoreactivity were increased, and alpha-SMA, PEDF and SOD3 immunoreactivity were decreased in the diabetic retina. The immunoreactivity of these markers was partially recovered in the AAV-SOD3 treated after STZ injection group. Parvalbumin expression was not decreased in the AAV-SOD3 treated after STZ injection group. In the diabetic retinas, the immunoreactivity of recoverin was weakly detected in both of the inner nuclear layer and inner plexiform layer compared to the control group but not in the AAV-SOD3 treated after STZ injection group.
Conclusions :
AAV-SOD3 after STZ injection treatment attenuated the loss of a/b-wave amplitudes in the diabetic rats, which was consistent with the immunohistochemical evaluation. AAV-SOD3 after STZ injection treatment ameliorated the retinal Muller cell, neuronal cell activation in diabetic rats and pericyte dysfunction. These results suggested that AAV-SOD3 after STZ injection exerted protective effects on the development of diabetic retinopathy.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.