Abstract
Purpose :
In our previous in vivo clinical and in vitro studies, we found that S100A9, a myeloid-derived protein, was associated with the severity of diabetic retinopathy and produced by activated microglia in the retina. The study was designed to understand the role of S100A9 in the retina. We used transgenic mice (gain-of-function) intended to have the hematopoietic cell-specific H2-K promoter directing expression of the myeloid-related protein S100A9Tg (S100 calcium-binding protein A9) and green fluorescent protein.
Methods :
We used 8-12 weeks of male and female wild-type (WT) and S100A9Tg (C57B6.FVB-Tg(H2-K-S100a9, GFP)1Gabr/Jmice for this study. The clinical ocular examinations were used for fundus photography and fluorescein angiography (FA). Electroretinography was carried out to assess retinal function. Retinal thickness was measured using image-guided spectral-domain optical coherence tomography (OCT) images. Retinal vascular changes were calculated using Singapore I Vessel Assessment (SIVA) analysis and trypsin digest. In addition, the retina was processed for flow cytometry and immunohistochemistry.
Results :
The S100A9Tg mice had significantly low body weight and skin lesions. Flow cytometry indicated increased S100A9 expression in the retina compared to the WT mice. SIVA analysis of S100A9Tg indicated decreased retinal arteriolar and venular caliber in the fundus photography. S100A9Tg retinas exhibit damaged cellular architecture across neural layers with vascular injury. The immunostained retina showed degenerative neuronal cells and loss of synapses vital to retinal function.
Conclusions :
S100A9 gain-in-function in the S100A9Tg mice retina indicated neurodegenerative and vascular abnormalities, suggesting a vital role in the retina.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.