Increased Susceptibility to Cerebral Microhemorrhages Is Associated With Imaging Signs
of Microvascular Degeneration in the Retina in an Insulin-Like Growth Factor 1 Deficient
Mouse Model of Accelerated Aging
Age-related cerebrovascular defects contribute to vascular cognitive impairment and
dementia (VCID) as well as other forms of dementia. There has been great interest
in developing biomarkers and other tools for studying cerebrovascular disease using
more easily accessible tissues outside the brain such as the retina. Decreased circulating
insulin-like growth factor 1 (IGF-1) levels in aging are thought to contribute to
the development of cerebrovascular impairment, a hypothesis that has been supported
by the use of IGF-1 deficient animal models. Here we evaluate vascular and other retinal
phenotypes in animals with circulating IGF-1 deficiency and ask whether the retina
mimics common age-related vascular changes in the brain such as the development of
microhemorrhages. Using a hypertension-induced model, we confirm that IGF-1 deficient
mice exhibited worsened microhemorrhages than controls. The retinas of IGF-1 deficient
animals do not exhibit microhemorrhages but do exhibit signs of vascular damage and
retinal stress such as patterns of vascular constriction and Müller cell activation.
These signs of retinal stress are not accompanied by retinal degeneration or impaired
neuronal function. These data suggest that the role of IGF-1 in the retina is complex,
and while IGF-1 deficiency leads to vascular defects in both the brain and the retina,
not all brain pathologies are evident in the retina.