Abstract Body: Introduction: Visual impairments occur frequently in patients with cerebrovascular disease, particularly with carotid artery disease, which contributes to the development of vascular contributions to cognitive impairment and dementias (VCID). However, patients with VCID usually do not realize their vision loss until the postoperative period to improve their arterial circulation. These visual difficulties can be caused by the effects of dementia on the brain or an eye condition. Our study aimed to determine if our mouse model of VCID shows retinal alterations in the eye.

Methodology: In our lab, we used the bilateral carotid artery stenosis model (BCAS) in aged mice as a model of VCID. We implanted a 0.16 mm diameter micro-coil in each carotid artery in 17-month-old C57BL/6 mice of both sexes. Mice were maintained for two months until they were used for experiments. Then, mice were tested for open field, elevated plus maze, tail suspension, and fear conditioning. After euthanasia, their eyes were analyzed by immunohistochemistry and electron microscopy.

Results: We did not find significant differences in velocity and distance moved in the open field test, nor the elevated plus maze and tail suspension, but we did observe that BCAS significantly reduced the percentage of freezing time, compared with sham mice. Examination of the retina of the experimental mice revealed that BCAS mice showed a significantly reduced (p=0.02) synaptic layer or outer plexiform layer (OPL) area in the outer retina, compared with sham mice. Interestingly, the OPL in the retina of BCAS mice showed a significant reduction of horizontal cell bodies (p=0.023), an increase in the rod (p=0.054) and cone (p=0.033) sprout length, loss of cone terminals (p=0.037) and a reduction of pre- and post-synaptic protein expression (p=0.06), compared with the retina of sham mice.

Conclusions: Our study indicates that BCAS mice exhibit cognitive impairment, specifically associated with conditioning memory. However, they do not show anxiety-like behavior. Furthermore, the eyes of BCAS mice show an ectopic distribution of rod and cone synapsis in the retina, which occurs with natural aging and consequently leads to vision loss. Thus, BCAS can exacerbate aging-associated phenotypes in the retina of aged mice. Our study is the first to report vision impairments in aged BCAS mice, which makes it a feasible model to identify the molecular mechanisms that govern visual impairments in VCID patients.