Wilson J. Heriot

Choroidal Neovascularization Can Digest Bruch's Membrane: A Prior Break is Not Essential

A novel form of retinal phototoxicity has facilitated investigation of the effect of retinal pigment epithelial (RPE) damage on the choriocapillaris of the rat. In response to isolated RPE injury, the choriocapillaris buds, digests the endothelial basement membrane, and projects pseudopodia that erode Bruchs membrane. The development of subretinal neovascularization in one of the rats demonstrates that breaks in Bruchs membrane may result from this lytic process and that neither degeneration of Bruchs membrane nor a preexisting break is essential for subretinal neovascularization to occur.

Cellular Processes Causing Defects in Bruch's Membrane Following Krypton Laser Photocoagulation

Krypton laser photocoagulation of the posterior fundus of the rat created white retinal lesions comparable with therapeutic burns in the human. Twenty-four hours after injury, the retinal pigment epithelium was destroyed and the majority of the endothelial cells survived. The choriocapillary lumen was occluded. Bruchs membrane was not fractured nor had it undergone thermal lysis in any area studied but choriocapillary endothelial cell buds invaded the choroidal side of Bruchs membrane. After seven days, cellular protrusions arising from retinal pigment epithelial cells traversed Bruchs membrane through full-thickness defects and entered the choroid. Although intense laser burns may destroy Bruchs membrane, we conclude from this data that many so-called breaks in Bruchs membrane following laser therapy are formed by cellular processes and are not caused primarily by laser coagulation.

Basal Infolding Density in the Normal Pigmented Rat

A variation in retinal pigment epithelial (RPE) basal infolding (BI) density in normal rats was observed and quantified. Serial electron micrographs of the midequatorial region of all quadrants from both eyes of litter-mate pigmented rats, 58 days old, were prepared. The lengths of BI and Bruchs membrane (BM) were determined by tracing enlarged micrographs to a Zeiss MOP-3 analyser. BI density per unit length of BM was assessed over the choriocapillary (CC) lumen, nucleated cytoplasma and intercapillary septum (ICS), and expressed as the dimensionless ratio BI/BM. Fenestrae were counted. The average BI/BM was 8.7; the BI/BM over the ICS, 6.1, was significantly lower than over the CC, 10.7 (P less than 0.001). BI/BM over the lumen and nucleated CC cytoplasm was the same. The number of fenestrae was not strongly associated with BI density (R2: 0.33). These data support the notion that the density of BI is related to diffusion within BM and is proportional to the distance from the CC lumen.

High-voltage electron microscopy in eye research. Experimental analysis of the retinal pigment epithelium and choriocapillaris.

The high-voltage electron microscope (HVEM) permits examination of sections much thicker (up to 1 micron) than those usually used in transmission electron microscopy, which are approximately 70 nm in thickness. Two examples of the utility of the HVEM in research on the ultrastructure of the retinal pigment epithelium (RPE) and choriocapillaris are given: the identification of intracytoplasmic tubules that arise from the basal plasma membrane of rat RPE cells; and the tracing of processes arising from choriocapillary endothelial cells during experimentally induced neovascularization. In each case HVEM provided information not easily obtained in routine thin sections.

Interactions between the Retinal Pigment Epithelium and the Choriocapillaris after Krypton Laser Photocoagulation

Retinal diseases involving the retinal pigment epithelial (RPE) cells and the choriocapillaris (CC) have various clinical manifestations. All, however, are accompanied by at least some changes in both the RPE cells and the CC. These changes can be classified into two broad categories: the first is an atrophic form, involving atrophy of both the RPE cells and the CC, while the second is an active form characterized by the development of choroidal subretinal neovascularization. Since atrophy occurs in the RPE cells and in the CC concomitantly, and since choroidal neovascularization is not seen in areas of atrophic RPE cells, there is reason to suspect that some interactions exist between the RPE cells and the CC. However, the nature of the interactions between the RPE cells and the vascular endothelium, as well as the factors determining whether the disease will take an atrophic or an active course, are not clearly understood.