Pericytes - The Missing Link In Choroidal Blood Flow Regulation?

Abstract

Purpose: : For ocular blood flow homeostasis, adjustment of the vessel diameter is the most crucial point. This diameter is regulated via extrinsic pathways involving the autonomic nervous system as well as intrinsic humoral and paracrine factors, involving e.g., nitric oxide and endothelin but also oxygen and CO2. The intrinsic humoral regulation is poorly understood, and the mechanisms of neurovascular coupling remain unclear even more in the retina than in the choroid. Pericytes are cells closely surrounding blood vessels. Although retinal pericytes are thought to be involved into adjustment of retinal vessel diameter, no similar pericyte system in the choroid has been reported. Pericytes in ocular tissues are poorly understood and might represent an important source for blood flow regulation under various aspects. The present data suggest an important role for choroidal pericytes in blood flow regulation.

Methods: : Choroidal and retinal wholemounts of Sprague Dolly rats were cryosectioned, followed by single- and double-immunhistochemistry against PGP9.5, NG2, and CD 146. For documentation, confocal laser-scanning microscopy and fluorescence microscopy was used.

Results: : In retinal wholemounts, around 4 to 7 pericytes per 100 µm² were counted. The average cell diameters reached 5-10 µm, with processes traceable up to 20 µm. In rat choroidal wholemounts, 7 to 10 pericytes/100 µm² were counted. Choroidal pericytes reached average cell diameters of 10x10 µm with processes sometimes reaching up to 80 µm at estimated vessel diameters of 20µm. Processes of pericytes in both ocular tissues surround blood vessels and were detected to co-localize the pericyte markers NG2 and CD146. PGP 9.5 positive profiles were found in close apposition to pericytes, suggesting innervation of the pericyte system by the autonomic nervous system.

Conclusions: : The massive layer of pericytes around the choroidal vasculature as well as the innervation of pericytes with PGP9.5 positive processes suggest a role of the pericyte system in autonomic choroidal blood flow regulation. The extent of engulfment outreaches what has been reported for the retinal circulation, however, as to whether choroidal pericytes are involved into autoregulatory mechanisms of the choroid remains to be investigated.

Keywords: immunohistochemistry • blood supply • intraocular pressure