Cerebral Hypoperfusion Causes Behavioral Changes and Impairs the Rod Photoreceptor Pathway in the Retina of Aged Mice.

Abstract

Gradual reduction of cerebral blood flow occurs with aging, and it is a major cause of vascular dementia, a group of dementias with a cerebrovascular component. Interestingly, patients who have suffered a vascular insult may develop retinopathy, which may occur as an early symptom of vascular dementia. Several rodent models using young animals have been generated to mimic retinopathy caused by cerebral hypoperfusion; however, given that aging is an important factor in developing vascular dementia and hypoperfusion retinopathy, we propose to use aged (17-month-old) mice in a model of cerebral hypoperfusion. In this model, we implant two metallic micro-coils (0.16 mm inner diameter) around both common carotid arteries. We found that two months after surgery, aged mice with bilateral carotid artery stenosis (BCAS) showed hyperactivity-like behavior, cognitive deficits, and demyelination, which are pathological features in patients with vascular dementia. We also found that the retina of BCAS mice showed important morphological changes, such as reduced area of the outer synaptic layer, retraction of rod photoreceptor terminals, and increased sprouting of rod bipolar cells. BCAS mice also showed reduced in vivo retinal responses to different light intensities. Our study is the first to propose using aged mice in a model of hypoperfusion retinopathy, which is relevant to identifying the molecular mechanisms underlying vision loss with cerebral hypoperfusion.