From pathobiology to the targeting of pericytes for the treatment of diabetic retinopathy

Abstract

Pericytes, the mural cells that constitute the capillaries along with endothelial cells, have been associated with the pathobiology of diabetic retinopathy; however, therapeutic implications of this association remain largely unexplored. Pericytes appear to be highly susceptible to the metabolic challenges associated with a diabetic environment, and there is substantial evidence that their loss may contribute to microvascular instability leading to the formation of microaneurysms, microhemorrhages, acellular capillaries, and capillary nonperfusion. Since pericytes are strategically located at the interface between the vascular and neural components of the retina, they offer extraordinary opportunities for therapeutic interventions in diabetic retinopathy. Moreover, the availability of novel imaging methodologies now allows for the in vivo visualization of pericytes, enabling a new generation of clinical trials that use pericyte tracking as clinical endpoints. The recognition of multiple signaling mechanisms involved in pericyte development and survival should allow for a renewed interest in pericytes as a therapeutic target for diabetic retinopathy.

Figure 1

Simultaneous in vivo imaging of vascular perfusion and fluorescent retinal pericytes using a two-channel, adaptive optics scanning laser ophthalmoscope (AOSLO). (A) Wide field HRA Spectralis image shows approximately 30° field of mouse retina. Superimposed on the fundus image are motion-contrast AOSLO fields demonstrating capillary perfusion with micron-level resolution. (B) Two-channel imaging using AOSLO in vivo. Channel 1 collects NIR motion contrast demonstrating capillary perfusion (magenta, moving blood cells), while channel 2 simultaneously images DsRed fluorescently-labeled pericytes (green). (C) 5° AOSLO field demonstrates the association of pericytes (green) with perfused capillaries (magenta). Montage is from a single capillary stratification. (Reprinted from Schallek et al., Morphology and topography of retinal pericytes in the living mouse retina using in vivo adaptive optics imaging and ex vivo characterization. Invest Ophthalmol Vis Sci. 2013;54:8237-8250 with permission. Copyright ARVO.) [117••].