Permeability of Regenerating and Atrophic Choriocapillaris in the Rabbit

Abstract

When rabbits receive intravenous injections of sodium iodate, large expanses of the retinal pigment epithelium are destroyed. The adjacent capillary bed, the choriocapillaris, atrophies in response to the loss of the pigment epithelium and then regenerates. This provides a model of the permeability of regenerating and atrophic choriocapillaris, which we studied using intravenously injected horseradish peroxidase and catalase. Regenerating capillaries were permeable to peroxidase but not catalase. The permeability to peroxidase was probably due to endothelial fenestrations, since catalase (which is larger than peroxidase and does not penetrate endothelial fenestrae) was retarded at interendothelial junctional complexes, indicating that they were intact. Atrophic choriocapillaries were impermeable to catalase but displayed a heterogeneous permeability to peroxidase.This was correlated with the presence or absence of fenestrae; capillary profiles lacking fenestrae retained peroxidase in their lumina, whereas if fenestrae were present the tracer penetrated into the pericapillary space. The observations indicate that: (1) the permeability of the regenerating choriocapillaris is qualitatively similar to the mature choriocapillaris, and (2) the atrophic choriocapillaris undergoes changes in permeability that are primarily correlated with the loss of endothelial fenestrae. The observations provide a functional correlate – change in permeability – for structural changes in choriocapillaris endothelium (thickening, loss of fenestrae) in response to destruction of the retinal pigment epithelium, which has been postulated to exert a trophic effect on these capillaries.

Vascular Endothelial Growth Factor Expression in the Retinal Pigment Epithelium Is Essential for Choriocapillaris Development and Visual Function

“…4 -7 Furthermore, localized chemical or mechanical destruction of the RPE in animal models results in atrophy of choroidal vessels, loss of endothelial fenestrations, and increased deposition of collagen in the choroid. 8 -10 These observations are consistent with ultrastructural studies that provide evidence for a continuous remodeling of the choroidal vessels in the adult, 9,10 with large vessels showing extensive fenestrations at the side facing the RPE. Thus, RPE cells have an essential role in the development and the maintenance of a fenestrated choroidal vasculature in the eye.…”

RPE barrier breakdown in diabetic retinopathy: seeing is believing

“…Overexpression of VEGF or its receptors is associated with DME [45][46][47]. Although the RPE is known to be important to the regulation of permeability for the RPE barrier [48], mechanistic studies on the function of the RPE barrier were carried out in RPE cultures supplemented with VEGF. However, in cultured ARPE-19 and RPE-51 cells, VEGF significantly upregulated ZO-1α + and ZO-1α − mRNA and proteins, resulting in a significant increase in their TER [49].…”

Final Report on the Safety Assessment of Sodium Iodate

“…Additional data on possible adverse ocular effects of Sodium Iodate, including (but not limited to) retinal, blood-retinal barrier, pigment epithelium, rhodopsin regeneration, and ERG effects, are available (Sorsby and Reading, 1964;Sorsby, 1966;Clifton and Makous, 1973;Davson, 1973;Flage, 1983;Amemiya, 1977;Nilsson et al, 1977a,b,c;Olsen et al, 1979;Ringvold, 1978;Textorius and Welinder, 1981;Campochiaro et al, 1986;Korte et at., 1986;Kitano et al, 1988;Taura and Reddy, 1988; Korte et al, 1989).…”