Roy W. Bellhorn

Epithelium-Capillary Interactions in the Eye: The Retinal Pigment Epithelium and the Choriocapillaris

Publisher Summary This chapter describes the evidence for epithelium–capillary interactions where the two are apposed, emphasizing structural and functional manifestations such as capillary permeability and cell polarity. The observations derived from human ocular histopathology and experimental animal models are focused in which interactions are evident between (1) the retinal-pigment epithelium (RPE) and its apposed capillary plexus, the choriocapillaris and (2) RPE and retinal capillaries experimentally brought into apposition with RPE, from which they are normally isolated. These observations are relevant to the pathogenesis of chorioretinal diseases like age-related macular degeneration and retinitis pigmentosa. The biology of the RPE-choriocapillaris interactions determines the relative contributions of ECM components, soluble factors, and phenotypically different types of RPE cells to observations made in situ. They are the two causes of reduced vision and blindness that arise at the RPE and lead to complicating secondary changes in the adjacent choriocapillaris and neural retina. The possible mechanisms of RPE–choriocapillaris interactions are also discussed in the chapter.

Refractive state, ocular anatomy, and accommodative range of the sea otter (Enhydra lutris).

Sea otters are carnivorous, amphibious mammals that are active both above and under water. Accordingly, it might be expected that their eyes are adapted for both aerial and aqueous vision. We examined the anatomy and physiological optics of the sea otter eye with a view towards describing and explaining its amphibious visual characteristics. We employed photokeratoscopy to measure the refractive power of the sea otter cornea, which we found to be 59 D. Using video dynamic photorefraction, we found that sea otters can focus targets clearly both in air and water, relying on accommodation to compensate for the refractive loss of their corneas upon immersion in water. Our anatomical investigations revealed that the anterior epithelium of the cornea is extensively developed, as is the iris musculature, meridional ciliary muscle, and the corneoscleral venous plexus. The first feature is most likely an adaptation to the salinity of the marine environment. We believe the latter features are part of a novel, well-developed lenticular accommodative mechanism.

Trace element status and free radical defense in elderly rhesus macaques (Macaca mulatta) with macular drusen

Abstract Research into the mechanisms underlying the development of age-related macular degeneration (AMD), the leading cause of visual loss in the United States and Europe in people over 60 years old, has been limited in part by the lack of animal models for this disease. In the current study, we examined 62 elderly (≥20 years old) rhesus macaques (Macaca mulatta) for the presence and severity of macular drusen. Drusen were observed in 47% of the macaques; they were similar histologically and in clinical appearance to the drusen observed in humans with AMD. It has been proposed that excessive tissue free radical damage may contribute to the development of AMD. Thus, circulating levels of select components of the free radical defense system and plasma thiobarbituric acid reactive substances (TBARS), an estimate of lipid peroxides, were measured in the above animals. Macaques diagnosed with drusen were characterized by alterations in concentrations and activities of several components of the free radical defense system. Alterations were most evident with respect to those enzymes associated with copper. The concept that excessive oxidative lipid damage might be a factor contributing to the occurrence of this disease is suggested by the findings of higher plasma TBARS concentrations in animals with > 10 drusen compared with animals without drusen.

Remodelling of the retinal pigment epithelium in response to intraepithelial capillaries: evidence that capillaries influence the polarity of epithelium

SummaryLight- and urethane-induced retinopathies in rats are characterized by loss of photoreceptors. Retinal capillaries subsequently become incorporated into the normally avascular retinal pigment epithelium. These models provided an opportunity to study the response of epithelial cells to closely apposed capillaries, in order to determine if capillaries contribute to the polar organization of epithelial cells. Pigment epithelial cells reorganized their lateral plasma membrane where the latter faced intraepithelial capillaries. This normally flat, undifferentiated membrane developed attachment sites, folds and intracytoplasmic tubules, and exhibited endocytosis and putative basal lamina secretion. These structural and functional specializations are normally restricted to the basal plasma membrane — the normal vascular front of the cell facing the dense meshwork of capillaries constituting the choriocapillaris. We conclude that RPE cells, and perhaps epithelia in general, polarize in response to an adjacent capillary bed.

Development of hereditary tapetal degeneration in the beagle dog

Laboratory beagle dogs with an apparent absence of a tapetum lucidum were identified by ophthalmoscopic examination. Breeding experiments demonstrated a probable autosomal recessive mutation. Studies of the development of the tapetal abnormality showed that up to postnatal day 21 the tapetum was normal by light and ultrastructural morphology. Subsequent to that time the tapetal rodlets failed to accumulate electron-dense material, did not accumulate zinc, and degenerated primarily into spherical inclusion bodies of varying electron density. In the early phases of the degeneration the rough endoplasmic reticulum formed large whorls of membrane denuded of ribosomes. With time, the inclusions became electron lucent, and the entire tapetal cell degenerated, ending with almost total loss of the tapetum lucidum by approximately one to two years of age. The structure of the retina was normal. Retinal function measured by electroretinography was normal except for a slight elevation of dark adapted white light thresholds. It is speculated that the hereditary defect may be defective synthesis of the tapetal rodlet matrix or of the zinc-complexing substance of the tapetum.

Retinal nutritive systems in vertebrates

The components of retinal nutritive systems show considerable variation throughout the vertebrates. In all species studies, there is a choroidal system that lies just sclerad (external) to the retina. Vitread (internal) epiretinal (or preretinal) systems are present in a variety of species, as are intraretinal vessel systems; complete lack of these latter two mentioned systems is also observed in some species. In this presentation, I describe the morphologic characteristics of retinal nutritive systems of fish, reptilian avian, and various mammalian species. A number of these variations are demonstrated photographically through the use of fundus photography. In particular, I describe and provide examples of holangiotic, merangiotic, paurangiotic, and anangiotic retinal vascular patterns within the eyes of mammalian species.

Melanosome abnormalities of ocular pigmented epithelial cells in beagle dogs with hereditary tapetal degeneration

Eyes of laboratory beagle dogs with an inherited tapetal degeneration were abnormally lightly pigmented. The development of pigmentation was followed morphologically from 7 days postnatal to 9 years of age. At all postnatal ages the iris pigmented epithelia contained no normal melanosomes, only organelles resembling secondary lysosomes or residual bodies. The ciliary body pigmented epithelium contained a variety of melanosome organelles at the earliest stages examined, but in fewer numbers than in normal animals. These included premelanosomes, partially melanized and some fully melanized pigment granules. However, the melanin deposition was usually patchy and irregular. With time, many of these granules appeared to condense into residual bodies. The retinal pigmented epithelium in peripheral and inferior posterior regions of affected animals never contained normal appearing melanin granules at any stage of postnatal development. The iris and choroidal stroma had melanosomes of normal size and shape, but many fewer than in normal animals. These results imply that there is local cellular control over melanosome production and regression, since the melanosome abnormalities do not follow the anterior to posterior development of pigment in ocular epithelia. It is proposed that a defect in synthesis of the matrix component of melanosomes could result in absent or abnormal deposition of melanin and initiate a process of autophagy of these organelles.

Experimental Evidence that Capillaries Influence RPE Polarity

When rats are exposed to fluorescent light or receive subcutaneous injections of urethane the photoreceptors degenerate and retinal capillaries move into the retinal pigment epithelium, or RPE (Bellhorn et al.,1973,1980). Here they become inserted between the lateral plasma membranes of adjacent RPE cells. This membrane, normally flat and undifferentiated, responds to the presence of the intraepithelial capillaries by developing structures and assuming functions that are normally restricted to the basal plasma membrane, i.e., that facing the choriocapillaris. In this article the changes in the lateral plasma membrane are described and presented as evidence that capillaries influence the structural and functional polarization of RPE cells. With our previous observation that the capillary segments apposed to RPE respond by losing their “retinal” characteristics (the endothelium thins, develops fenestrae and becomes permeable to horseradish peroxidase; they become choriocapillaris-like: Bellhorn et al.,1973,1980; Korte et al., 1983) these observations show that RPE and capillaries interact. These interactions probably contribute to homeostasis at the RPE-choriocapillaris interface in the normal retina. An upset in these interactions may contribute to the development of retinal disease, e.g., by permitting neovascularization or altering the blood-retinal barrier.

Snake spectacle vessel permeability to sodium fluorescein

OBJECTIVE Assess vascular permeability of the snake spectacle to sodium fluorescein during resting and shedding phases of the ecdysis cycle. ANIMAL STUDIED Ball python (Python regius). PROCEDURES The snake was anesthetized, and spectral domain optic coherence tomography was performed prior to angiographic procedures. An electronically controlled digital single-lens reflex camera with a dual-head flash equipped with filters suitable for fluorescein angiography was used to make images. Sodium fluorescein (10%) solution was administered by intracardiac injection. Angiographic images were made as fluorescein traversed the vasculature of the iris and spectacle. Individually acquired photographic frames were assessed and sequenced into pseudovideo image streams for further evaluation CONCLUSIONS: Fluorescein angiograms of the snake spectacle were readily obtained. Vascular permeability varied with the phase of ecdysis. Copious leakage of fluorescein occurred during the shedding phase. This angiographic method may provide diverse opportunities to investigate vascular aspects of snake spectacle ecdysis, dysecdysis, and the integument in general.