According to updated clinical guidelines, approximately 50% of adults in the U.S. have hypertension, a major risk factor for end organ damage, including injury to the retinal microvasculature. Pericytes are important cells of the microvasculature, supporting capillary stability, endothelial cell (EC) function, and blood-retinal barrier integrity. However, little is known about how they are impacted by chronically high blood pressure. We hypothesized that hypertension would reduce pericyte coverage in the retinal microvasculature, which would then contribute to capillary rarefaction. Retinas were collected from 4- to 6-month-old male and female BPH/2J hypertensive mice (n=5) and their age-matched normotensive control, BPN/3J mice (n=4). Eyes were enucleated, fixed, and processed for whole-mount immunofluorescence using neural/glial antigen 2 (NG2) for pericytes, CD31 (PECAM-1) for EC, and DAPI as a nuclei marker. Pericytes and vascular architecture were investigated by confocal microscopy. Pericytes were counted and averaged from three different regions of interest per retina, with specific criteria used to select the mid-peripheral retina (or intermediate zone), between the optic nerve and the periphery for analysis. Retinal whole mounts were used to assess capillary area (%) through ImageJ. Data were analyzed using two-tailed, unpaired Student’s t -tests (p<0.05). Hypertensive BPH/2J mice exhibited a significant reduction in pericyte number per field of view (#) compared to BPN/3J controls (BPH/2J: 2.3±0.2 vs. BPN/3J: 4.8±0.4, p=0.0007). There were also noticeable changes to the vascular architecture. Specifically, capillary area was significantly decreased in BPH/2J mice compared to BPN/3J mice (BPH/2J: 29.3±3.9% vs. BPN/3J: 59.0±4.3%, p=0.0014). These preliminary findings indicate that essential hypertension reduces pericyte coverage and induces capillary rarefaction in the retinal microvasculature, possibly contributing to early microvascular remodeling associated with hypertensive retinopathy.
Nampoothiry et al. (Mon,) studied this question.