Hedva Miller

Experimental Epiretinal Proliferation Induced by Intravitreal Red Blood Cells

We describe a reproducible animal model of epiretinal proliferation, based on intravitreal injection of red blood cells, that closely simulates the more benign proliferative extraretinopathies. Using light microscopy and scanning and transmission electron microscopy, we monitored the development and behavior of the experimental epiretinal membranes. We found breaks in the integrity of the retinal surface through which glial cells migrated onto the retina, proliferated into thick epiretinal tissue, and contracted to cause retinal pucker. All these steps were associated with the chronic inflammatory response to the long-lasting presence of red blood cells in the vitreous. Thus, the development of epiretinal membranes requires continuous intraocular stimulation in addition to a break in retinal integrity.

Correlation of Choroidal Subretinal Neovascularization With Fluorescein Angiography

The presence and distribution of laser-induced experimental subretinal neovascularization were studied by serial reconstruction and correlated with the amount of fluorescein leakage during angiography. All laser lesions that demonstrated leakage and pooling of fluorescein (leaky lesions) contained subretinal vessels with an overlying fluid-filled space. The subretinal vessels extended beyond the area of demonstrated leakage, while the fluid-filled space overlying the subretinal vessels correlated closely with the demonstrated area of leakage. All leaky lesions gradually stopped leaking fluorescein, that is, involuted. The disappearance of leakage was not accompanied by a reduction in the number of subretinal vessels but rather with the disappearance of the overlying fluid. Further, 80% of the lesions that never leaked fluorescein (nonleaky lesions) also contained subretinal vessels but no overlying fluid. Our findings indicate that subretinal vessels can be detected by fluorescein angiography only if they lie beneath a fluid-filled space.

Effect of the vitreous on retinal wound-healing

The healing process of experimental retinal wounds in nonvitrectomized and vitrectomized rabbit eyes was compared. Using light, transmission and scanning electron microscopy, a significant difference was observed at the late stages of the healing process. The retinal wounds in the nonvitrectomized eyes healed properly, forming regular and smooth scars, while the scars that developed in the vitrectomized eyes were irregular and hypertrophic. Our observations suggest that the vitreous plays a role in normal healing of retinal wounds.

Mechanisms of Lumen Formation: Morphologic Observations on Experimental Subretinal Neovascularization

Using light and electron microscopy, we studied the sequence of events that lead to the formation of new vascular lumens after laser photocoagulation of the retina and choroid of primates. Three days after photocoagulation, not only the endothelial cells in pre-existing vessels but also those in re-endothelialized vessels showed budding and lumen formation. The lumen of vessels was formed by the budding of adjacent endothelial cells that were coupled by transient intercellular junctions.

Involution of Subretinal Neovascularization

Subretinal neovascularization (SRN) is a pathologic feature of many eye diseases (1). For example, it accounts for more than 80% of severe visual loss associated with macular degeneration (2). The newly formed vessels proliferate from the choroid into the subretinal space and are diagnosed by fluorescein leakage during angiography (3,4). In both humans (4) and animal models of subretinal neovascularization (5) this leakage persists for only a certain period of time, after which it diminishes gradually until it disappears completely and staining of the scar only is seen on the angiogram. This process is defined as involution of the subretinal membrane.