Blood Vessel Changes in the Eyes Linked with Lung Vascular Damage in PAH, Study Finds

A type of abnormality in small blood vessels of the eyes, called retinal vascular tortuosity, may provide a non-invasive way to detect alterations in lung circulation in patients with pulmonary arterial hypertension (PAH), according to a new study.

The research, “Retinal Vascular Tortuosity, a New Feature of Systemic Manifestation of Pulmonary Arterial Hypertension,” was presented at the 2019 American Thoracic Society (ATS) Conference in Dallas, Texas, May 17-22.

PAH is characterized by pulmonary vascular remodeling, and patients with an altered cellular signaling mediated by the BMPR-2 receptor are known to have abnormalities in systemic circulation, including in blood vessels of the eye. Altered circulation in the eye’s retina is associated with dysfunctional coronary microvessels — the smallest blood vessels in the body — in patients with left heart disease, which is the most common cause of PH.

Now, scientists at Stanford Hospital and Clinics and Stanford Medical Center hypothesized that pulmonary and retinal microvascular endothelial cells (mvECs) — those lining the blood vessels — lacking BMPR2 have similar changes. They also hypothesized that retinal microvascular alterations are present in both an animal model of PH and in PAH patients, as part of a systemic vascular defect.

Researchers suppressed the BMPR-2 gene in pulmonary and retinal mvECs. The gene expression of these cells was assessed, and changes in microvessel tortuosity were analyzed in the retinas. Retinal imaging also was conducted in two PAH patients without other significant cardiovascular comorbidities, and in two healthy controls.

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Results revealed that BMPR-2 gene suppression, or “knock-down,” led to similar defects in angiogenesis (blood vessel formation) in both pulmonary and retinal cells.

Thirty-seven of 84 angiogenesis-related genes showed similar regulation in pulmonary and retinal cells. BMPR-2 suppression resulted in lower levels of the proteins FGFR3, PDGFB, TGFBR1, EFNA1, EFNAB2, ID1, and COL4A3, and increased level of angiopoietin-2 (Ang2) during angiogenesis in both pulmonary and retinal mvECs.

Animals exposed to hypoxia — oxygen deficiency — had higher right ventricular systolic pressures, which significantly correlated with greater retinal microvessel tortuosity. Similar results were seen in PAH patients, as their retinas also had increased microvessel tortuosity compared with the controls.

Overall, the data indicate that retinal vascular tortuosity is linked to pulmonary vascular remodeling, a PAH hallmark, suggesting that the eye may offer useful information about the patient’s pulmonary circulation status.

“In animals and humans, pulmonary hypertension was associated with an increase in retinal microvascular tortuosity,” the scientists wrote.

“Pulmonary and retinal vascular changes might be closely related due to a similar angiogenic gene response in mvECs after BMPR-2 knockdown, therefore causing changes in both microcirculations,” the team suggested.