The effect of CysLTR1 inhibition on cells of the retinal neurovascular unit in 5xFAD Alzheimer mice

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease that affects both the brain and the retina. Many cerebral-associated AD pathologies, including neuroinflammation and vascular changes, have been reported to manifest in the retina. Furthermore, the neurovascular unit (NVU), composed of vascular cells, glia and neurons, regulates blood flow and neuronal metabolic activity and has been described to be dysfunctional in AD brains and retinas. As leukotrienes are modulators of both neuroinflammation and the vasculature, their receptors have been recognized as potential targets for ameliorating AD pathology. Therefore, the present study investigated the effects of the cysteinyl leukotriene receptor 1 (CysLTR1) antagonist montelukast (MTK) on retinal NVU cells in the 5xFAD mouse model of AD. Retinal analyses were performed in male and female 8-month-old 5xFAD mice and after 13-weeks of treatment with low and high doses of MTK or vehicle, and in age-matched controls. The retinal pericyte (PC) coverage was unchanged in AD, but CysLTR1 inhibition resulted in increased PC coverage in AD mice. Furthermore, an AD-associated decrease in capillary diameter was observed, which was not affected by CysLTR1 inhibition. The number of retinal microglial cells was increased in AD, independent of treatment. In addition, the astrocyte area and retinal ganglion cell density were not affected by either AD or CysLTR1 inhibition. In conclusion, the present study revealed minor AD-associated changes in retinal NVU cells in the 5xFAD mouse model. MTK treatment increased dose-independently PC coverage, but it remains to be clarified whether this affects the vessel tightness and blood flow.