Pathomechanisms of Cystoid Macular Edema

Abstract

Cystoid macular edema (CME) is a well-known endpoint of various ocular diseases, but the relative pathogenic impact of extra- and intracellular fluid accumulation within the retinal tissue still remains uncertain. While most authors favor an extracellular fluid accumulation as the main causative factor of cyst formation, there are indications that Müller cell swelling may also contribute to CME development (particularly in cases without significant angiographic vascular leakage). Vascular leakage occurs after a breakdown of the blood-retinal barrier during traumatic, vascular, and inflammatory ocular diseases, and allows the serum to get into the retinal interstitium. Since intraretinal fluid distribution is restricted by two diffusion barriers, the inner and outer plexiform layers, serum leakage from intraretinal vessels causes cysts mainly in the inner nuclear layer while leakage from choroid/pigment epithelium generates (in addition to subretinal fluid accumulation) cyst formation in the Henle fiber layer. In the normal healthy retina, the transretinal water fluxes are mediated by glial and pigment epithelial cells. These water fluxes are inevitably coupled to fluxes of osmolytes; in the case of glial (Müller) cells, to K⁺ clearance currents. For this purpose, the cells express a complex, microtopographically optimized pattern of transporters and channels for osmolytes and water in their plasma membrane. Ischemic/hypoxic alterations of the retinal microvasculature result in gliotic responses which involve down-regulation of K⁺ channels in the perivascular Müller cell end-feet. This means a closure of the main pathway which normally generates the osmotic drive for the redistribution of water from the inner retina into the blood. The result is an intracellular K⁺ accumulation which, then, osmotically drives water from the blood into the glial cells (i.e., in the opposite direction) and causes glial cell swelling, edema, and cyst formation. While the underlying mechanisms await further research, it is expected that their improved knowledge will stimulate the development of novel therapeutic approaches to resolve edema in retinal tissue.