(The) non-axonal posterior circulation of the intravitreal ovalbumin through the ONH and ISVP

Abstract

Ocular circulation was known as separated two circulations, anterior and posterior circulation. In anterior circulation, there is trabecular and uveoscleral outflow. However, posterior circulation has not been fully understood yet. Some molecules including human amyloid-beta 1-42 can pass through the directly optic nerve via the lamina cribrosa (LC) mesh-like membranous structure at the same level as the sclera. But it is still elusive that understand the pathway of the non-axonal transported molecules such as ovalbumin (OVA) and dextran which is not able to pass the optic nerve. Herein, we revealed the route of the posterior circulation pathways to OVA. Uptake signals of the intravitreally injected OVA in CX3CR1-GFP+ cells were accumulated at the optic nerve head (ONH) and connected from the superficial retina to ONH until in front of the LC. Although any OVA signal wasn’t detected in an optic nerve and the RPE layer, uptake signals of OVA in CX3CR1-GFP+ cells were connected to choroidal layers. The central retinal vein from the proximal retinal vein to the retinal vein of the ONH has increased PLVAP (Plasma lemma vesicle-associated protein) expression even in healthy mice. Uptake signals of the OVA continued to the peripheral choroid and intra-scleral venous plexus (ISVP), which is connected between the conjunctiva and choroid. And any signals wasn’t detected in the Schlemm’s canal most common pathway of the anterior circulation. Finally, intravitreally injected OVA was detected in typical lymphatics of the conjunctiva and superficial cervical lymph nodes via ISVP. Vice versa, subconjunctivally injected molecules such as ovalbumin, amyloid beta and lectin was also detected in the choroidal layers and the subconjunctival clodronate liposome depletion worked in choroidal macrophages. However, uptake signals of OVA were different by methods respectively, intravitreal and intravenous injection. The subconjunctivally and intravitreally injected ovalbumin can’t be found in the vortex vein, although intravenous clodronate liposome didn’t work for the choroidal macrophages. Our data showed the existence of a non-axonal molecular transport pathway which is independent to systemic choroid circulation, providing new insight for understanding the posterior circulation related to the pathophysiology of the ONH and ISVP.