Angiostatin in the primate retina: A causal factor of foveal avascularity?

Abstract

Purpose : The primate retina is characterized by the fovea avascular zone (FAZ) and the well-defined perifoveal capillary plexus. Neither blood vessels nor their accompanying astrocytes enter the fovea during any stage of retinal development; a balance of angiogenic and angiostatic factors probably maintains foveal avascularity throughout life. The aim of this study was to identify the angiorepulsive factors involved in the development of the avascular primate retinal fovea.

Methods : Retinas of newborn, juvenile, and adult Callithrix jacchus and Macaca fascicularis monkeys were studied to determine the localization of angiostatin in relation to the III β-tubulin positive ganglion cells, glial fibrillary acidic protein positive glia, vascular endothelial growth factor (VEGF) positive glia, Iba-1 positive microglia, and the angiostatin receptor αvβ3-integrin capillaries. Expression studies were performed using immunohistochemistry (IHC) on retinal whole-mount and paraffin sections, and western blotting on frozen material.

Results : As expected, a complex network of the main retinal cell types was identified by IHC of retinal whole mounts. In general, lifetime expression of angiostatin was found in all retinas. Colabeling with aforementioned different markers revealed retinal ganglion cells as the main source of angiostatin expression in the primate retinas examined, whereas blood capillaries expressed the angiostatin receptor αvβ3-integrin and capillary-associated astrocytes expressed VEGF. The FAZ was free of microglia cells.

Conclusions : This study provides the first evidence of angiostatin expression in the primate retina. The elevated expression of angiostatin in the foveal region relative to the perifoveal macular and peripheral retina suggests that angiostatin plays a role in the repulsion of perifoveal capillaries, and provides an explanation for the development and persistence of an avascular fovea.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.