Ocular Vascular Endothelial Heterogeneity

Endothelial cells form the lining of the vasculature. Despite the continuity of this layer throughout the body, endothelial cells exhibit remarkable heterogeneity in structure, molecular composition and activity: between sites; and in response to different exposures. One important consequence of endothelial diversity is the localized nature of many vascu- lar disorders. To date a limited number of studies have attempted to define unique phenotypic features of the different in- traocular endothelial subpopulations, which include the endothelial cells of vascular beds in the iris, the choroid and the retina. Differences that distinguish endothelial cells in the circulations of the choroid and the retina, in particular, are be- lieved to be major etiological factors controlling the specific involvement of the two tissues in some of the most common blinding diseases. Age-related macular degeneration involves choroid, and diabetic retinopathy and posterior uveitis are primarily diseases of the retina. Development of effective targeted therapies for these ocular disorders will require a de- tailed understanding of the heterogeneity of ocular endothelia. Our review summarizes the existing literature relating to diversity of the ocular endothelial cells. We highlight structural, metabolic and functional characteristics that distinguish intraoocular endothelial subtypes from each other and from extraocular endothelial cells, and we consider the implications of these differences for the design of novel biological therapeutics for eye diseases.