Retinal Oxygen Metabolism Research Articles

Metabolic physiology in age related macular degeneration

Ischemia and hypoxia have been implicated in the pathophysiology of age related macular degeneration (AMD). This has mostly been based on studies on choroidal perfusion, which is not the only contributor to retinal hypoxia found in AMD eyes. Other features of AMD may also interfere with retinal oxygen metabolism including confluent drusen, serous or hemorrhagic retinal detachment, retinal edema and vitreoretinal adhesion. Each of these features contributes to retinal hypoxia: the drusen and retinal elevation by increasing the distance between the choriocapillaris and retina; vitreoretinal adhesion by reducing diffusion and convection of oxygen towards and vascular endothelial growth factor (VEGF) away from hypoxic retinal areas. Hypoxia-inducible-factor is known to exist in subretinal neovascularization and hypoxia is the main stimulus for the production of VEGF. Each feature may not by itself create enough hypoxia and VEGF accumulation to stimulate wet AMD, but they may combine to do so. Choroidal ischemia in AMD has been demonstrated by many researchers, using different technologies. Choroidal ischemia obviously decreases oxygen delivery to the outer retina. Confluent drusen, thickening of Bruch's membrane and any detachment of retina or retinal pigment epithelium, increases the distance between the choriocapillaris and the retina and thereby reduces the oxygen flux from the choroid to the outer retina according to Fick's law of diffusion. Retinal elevation and choroidal ischemia may combine forces to reduce choroidal oxygen delivery to the outer retina, produce retinal hypoxia. Hypoxia leads to production of VEGF leading to neovascularization and tissue edema. A vicious cycle may develop, where VEGF production increases effusion, retinal detachment and edema, further increasing hypoxia and VEGF production. Adhesion of the viscous posterior vitreous cortex to the retina maintains a barrier to diffusion andconvection currents in the vitreous cavity according to the laws of Fick's, Stokes-Einstein and Hagen-Poiseuille. If the vitreous is detached from the surface of the retina, the low viscosity fluid transports oxygen and nutrients towards an ischemic area of the retina, and cytokines away from the retina, at a faster rate than through attached vitreous gel. Vitreoretinal adhesion can exacerbate retinal hypoxia and accumulation of cytokines, such as VEGF. Vitreoretinal traction can also cause hypoxia by retinal elevation. Conceivably, the basic features of AMD, drusen, choroidal ischemia, and vitreoretinal adhesion are independently determined by genetics and environment and may combine in variable proportions. If the resulting hypoxia and consequent VEGF accumulation crosses a threshold, this will trigger effusion and neovascularization.

Oxygen supply and consumption in the retina: implications for studies of retinopathy of prematurity

A disrupted oxygen environment in the retina of severely premature neonates is thought to be a key factor in the development of retinopathy of prematurity (ROP). This review describes our understanding of intraretinal oxygen distribution and consumption in a range of animal models, including species with naturally avascular retinas and models of induced occlusion of the retinal vasculature. The influence of graded systemic hyperoxia on retinal oxygenation is also discussed along with modulation of retinal oxygen metabolism. The differences in retinal oxygenation between developing and mature retinas are also described. Comparisons are made with studies in the monkey retina in order to assess possible similarities in behaviour between rat and human retinas. Pathogenesis mechanism and possible intervention strategies during the diseased processes in ROP are proposed based on our current knowledge.

Noninvasive oximetry and glaucoma

Abstract Purpose To investigate retinal vessel oxygen saturation in relation to glaucomatous visual field damage. Specifically, we examined whether oxygen saturation in retinal blood vessels differs between regions corresponding to glaucomatous visual field defects compared to regions without visual field defects. Methods A spectrophotometric retinal oximeter (Oxymap ehf, Reykjavík, Iceland) was used to measure oxygen saturation in retinal arterioles and venules. The oximeter consists of a fundus camera, beam splitter, light filters and software that evaluate the oxygen saturation. The glaucomatous defect was estimated from a visual field test using the Octopus 1‐2‐3 perimeter. One eye in 13 individuals with open angle glaucoma with or without pseudoexfoliation syndrome was examined. Results In retinal areas with no visual field defect, the mean oxygen saturation in arterioles was 102±6% and 65±9%, (mean±SD) in venules. The arteriovenous difference was 37±10%. In retinal areas corresponding to visual field defects, the mean oxygen saturation in arterioles was significantly lower; 98±5% (p=0.04, paired t‐test, n=13). The venules were at 68±7% (p=0.3) and the arteriovenous difference was also significantly lower; 30±10% (p=0.04). Conclusion Arteriolar oxygen saturation and arteriovenous difference is statistically lower in areas with visual field defects compared to areas without visual field defects. This data suggests that visual field defects are associated with a reduction in retinal oxygen delivery and metabolism.

Retinal Oxygenation and Oxygen Metabolism in Abyssinian Cats with a Hereditary Retinal Degeneration

To investigate the effects of a hereditary retinal degeneration on retinal oxygenation and determine whether it is responsible for the severe attenuation of retinal circulation in hereditary photoreceptor degenerations. Seven adult Abyssinian cats affected by hereditary retinal degeneration were studied. Oxygen microelectrodes were used to collect spatial profiles of retinal oxygenation in anesthetized animals. A one-dimensional model of oxygen diffusion was fitted to the data to quantify photoreceptor oxygen utilization (Qo(2)). Photoreceptor Qo(2) progressively decreased until it reached zero in the end stage of the disease. Average inner retinal oxygen tension remained within normal limits at all disease stages, despite the observed progressive retinal vessel attenuation. Light affected photoreceptors normally, decreasing Qo(2) by approximately 50% at all stages of the disease. Loss of photoreceptor metabolism allows choroidal oxygen to reach the inner retina, attenuating the retinal circulation in this animal model of retinitis pigmentosa (RP) and probably also in human RP. As the degeneration progresses, there is a strong relationship between changes in the a-wave of the ERG and changes in rod oxidative metabolism, indicating that these two functional measures change together.

A microelectrode for measuring intracellular PO2.

A simple and reliable method of constructing an intracellular pH microelectrode is described. Antimony is used as the pH sensor. Antimony electrodes have been used in biological systems as early as 1927 (1). Since then several investigators have used different kinds of Sb electrodes. Roos and Boton (3) describe the latest methods of construction and application of pH sensitive micro-electrodes. In most cases the pH electrodes were fabricated by pulling glass capillaries filled with molten antimony and in a few cases by coating glass with antimony. The electrodes were of the open type.