Maintenance of an adequate oxygen supply to the retina is critical for retinal function.
In species with vascularised retinas, such as man, oxygen is delivered to the retina
via a combination of the choroidal vascular bed, which lies immediately behind the
retina, and the retinal vasculature, which lies within the inner retina. The high-oxygen
demands of the retina, and the relatively sparse nature of the retinal vasculature,
are thought to contribute to the particular vulnerability of the retina to vascular
disease. A large proportion of retinal blindness is associated with diseases having
a vascular component, and disrupted oxygen supply to the retina is likely to be a
critical factor. Much attention has therefore been directed at determining the intraretinal
oxygen environment in healthy and diseased eyes. Measurements of oxygen levels within
the retina have largely been restricted to animal studies in which oxygen sensitive
microelectrodes can be used to obtain high-resolution measurements of oxygen tension
as a function of retinal depth. Such measurements can immediately identify which retinal
layers are supplied with oxygen from the different vascular elements. Additionally,
in the outer retinal layers, which do not have any intrinsic oxygen sources, the oxygen
distribution can be analysed mathematically to quantify the oxygen consumption rate
of specific retinal layers. This has revealed a remarkable heterogeneity of oxygen
requirements of different components of the outer retina, with the inner segments
of the photoreceptors being the dominant oxygen consumers. Since the presence of the
retinal vasculature precludes such a simple quantitative analysis of local oxygen
consumption within the inner retina, our understanding of the oxygen needs of the
inner retinal components is much less complete. Although several lines of evidence
suggest that in the more commonly studied species such as cat, pig, and rat, the oxygen
demands of the inner retina as a whole is broadly comparable to that of the outer
retina, exactly which cell layers within the inner retina have the most stringent
oxygen demands is not known. This may be a critical issue if the cell types most at
risk from disrupted oxygen supply are to be identified. This paper reviews our current
understanding of the oxygen requirements of the inner and outer retina and presents
new data and mathematical models which identify three dominant oxygen-consuming layers
in the rat retina. These are the inner segments of the photoreceptors, the outer plexiform
layer, and the deeper region of the inner plexiform layer. We also address the intriguing
question of how the oxygen requirements of the inner retina are met in those species
which naturally have a poorly vascularised, or even totally avascular retina. We present
measurements of the intraretinal oxygen distribution in two species of laboratory
animal possessing such retinas, the rabbit and the guinea pig. The rabbit has a predominantly
avascular retina, with only a narrow band of retinal vasculature, and the guinea pig
retina is completely avascular. Both these animals demonstrate species adaptations
in which the oxygen requirement of their inner retinas are extremely low when compared
to that of their outer retinas. This finding both uncovers a remarkable ability of
the inner retina in avascular species to function in a low-oxygen environment, and
also highlights the dangers of extrapolating findings from avascular retinas to infer
metabolic requirements of vascularised retinas. Different species also demonstrate
a marked diversity in the manner in which intraretinal oxygen distribution is influenced
by increases in systemic oxygen level. In the vascularised rat retina, the inner retinal
oxygen increase is muted by a combination of increased oxygen consumption and a reduction
of net oxygen delivery from the retinal circulation. The avascular retina of the guinea
pig demonstrated a novel and powerful regulatory mechanism that prevents any dramatic
rise in choroidal oxygen levels and keeps retinal oxygen levels within the normal
physiological range. In contrast, in the avascular regions of the rabbit retina the
choroidal oxygen level passively follows the increase in systemic oxygenation, and
there is a dramatic rise in oxygen level in all retinal layers. The presence or absence
of oxygen-regulating mechanisms may well reflect important survival strategies for
the retina which are not yet understood. Intraretinal oxygen measurements in rat models
of retinal disease are also presented. We describe how oxygen distribution across
the rat retina is influenced by manipulation of systemic blood pressure. We examine
the effect of acute and chronic occlusion of the retinal vasculature, and explore
the feasibility of meeting the oxygen needs of the ischemic retina from the choroid.
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