Retinal oxygenation and oxygen metabolism in Abyssinian cats with a hereditary retinal degeneration

PURPOSE. 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. METHODS. 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 ). RESULTS. 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 ϳ50% at all stages of the disease. CONCLUSIONS. 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. 2-6 We hypothesized that the pronounced vasoconstriction results from decreased oxygen utilization by the outer retina after photoreceptor loss. Because less choroidal oxygen is used by the photoreceptors, it should reach the inner retina, where oxygen is known to cause constriction of retinal vessels. 10 Vessels do not simply constrict. Eventually they are lost in animals with photoreceptor degenerations. 6 These studies suggest not only a physiological role of oxygen, but a trophic (or antitrophic) one as well. In the present study, we further examined the hypothesis that oxygen from the choroid is responsible for attenuation of the retinal circulation, by characterizing changes in retinal oxygenation and oxidative metabolism during the progression of a feline hereditary retinal degeneration in a colony of Abyssinian cats. 3 The autosomal recessive genetic defect in this animal is not yet known, but it exhibits a slow rod-cone degeneration similar to human RP. Using measurements of intraretinal oxygen tension (PO 2 ) in these animals and our mathematical model of oxygen diffusion and utilization, 13 A preliminary report of these results has been presented (Linsenmeier RA, et al. IOVS 2000;41:ARVO Abstract 4721). METHODS Animals Eight Abyssinian cats affected by a hereditary retinal degeneration were studied. These are the same cats in which an ERG study, reported in this issue, was also performed. 13 3,13 The hematocrit from one stage 3 animal was low because of surgical complications and continued to decrease during the experiment. In this animal, the earlier choroidal PO 2 and the inner retinal PO 2 , which were in the normal range, are included in the reported data, but oxygen consumption data and later choroidal PO 2 data from this animal were not used. Electrode problems prevented data collection in one stage 2 animal. Data from animals with retinal degeneration were compared to similar data obtained from normal cats

A combined method to quantify the retinal metabolic rate of oxygen using photoacoustic ophthalmoscopy and optical coherence tomography

Quantitatively determining physiological parameters at a microscopic level in the retina furthers the understanding of the molecular pathways of blinding diseases, such as diabetic retinopathy and glaucoma. An essential parameter, which has yet to be quantified noninvasively, is the retinal oxygen metabolic rate (rMRO(2)). Quantifying rMRO(2) is challenging because two parameters, the blood flow rate and hemoglobin oxygen saturation (sO(2)), must be measured together. We combined photoacoustic ophthalmoscopy (PAOM) with spectral domain-optical coherence tomography (SD-OCT) to tackle this challenge, in which PAOM measured the sO(2) and SD-OCT mapped the blood flow rate. We tested the integrated system on normal wild-type rats, in which the measured rMRO(2) was 297.86 +/- 70.23 nl/minute. This quantitative method may shed new light on both fundamental research and clinical care in ophthalmology in the future

Oxygen distribution in the macaque retina

Purpose. Oxygen distribution was characterized in the macaque retina, which is more like the human retina than others studied previously. Methods. Profiles of oxygen tension (Po 2 ) as a function of distance were recorded in a parafoveal region about halfway between the fovea and optic disk, and from the fovea in one animal. A one-dimensional diffusion model was used to determine photoreceptor oxygen consumption (QO 2 ). Results. In the parafovea, the Po 2 decreased as the electrode was withdrawn from the choroid toward the inner retina, reaching a minimum value during dark adaptation of about 9 mmHg at about 70% retinal depth, and then increasing more proximally. Approximately 90% of the oxygen requirement of the photoreceptors was supplied by the choroidal circulation and 10% by the retinal circulation. In light adaptation, there was a monotonic Po 2 gradient from the choroid to the inner retina, indicating that all of the oxygen used by photoreceptors was supplied by the choroid. In the fovea, the choroid supplied almost all the oxygen in both dark and light adaptation, with a minor supply from the vitreous humor. Dark-adapted foveal oxygen consumption was lower than parafoveal oxygen consumption. Light reduced the oxygen consumption of the photoreceptors, in both regions studied, by 16-; Conclusions. The results show that oxygenation of the parafoveal monkey retina is similar to that previously observed in the cat area centralis. In the fovea, the oxygen distribution differs as expected considering the thinner retina and the absence of inner retinal neurons and retinal circulation. Invest Ophthalmol Vis Sci. 1993;34:516-521. Intensive measurements of oxygen distribution and photoreceptor oxygen consumption have been made in the retina of the cat 1 " 3 and miniature pig; 4 however, no intraretinal measurements, and only a small number of vitreal measurements, have been made in primates. In this paper, we report intraretinal measurements from two monkeys, and show that the cat retina : July 6, 1992; accepted November 10, 1992. Proprietary interest category: N. Reprint requests: Dr. Robert A. Linsenmeier, Biomedical Engineering Department, Northwestern University, 2145 serves as a good model for oxygenation of the parafoveal primate retina. In one monkey, we were able to obtain measurements from the fovea. These measurements showed differences that were consistent with the decreased retinal thickness and the absence of retinal circulation in this region. MATERIALS AND METHODS Measurements were made from two monkeys using techniques that were similar to those used previously in studies on the cat. 25 One monkey was a cynomolgus macaque (M. fascicularis) weighing 3.3 kg and the other was a pig-tailed macaque (M. nemestrina) weighing 4.8 kg. We adhered to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Animals were initially anesthetized with keta- 51

Resistance of diabetic rat electroretinogram to hypoxemia. Invest Ophthalmol Vis Sci.

-f Purpose. To investigate the mechanisms of the known electroretinographic abnormalities of diabetic rats and to explore effects of hypoxemia. Methods. Subretinal and vitreal microelectrodes were used to isolate the retinal and retinal pigment epithelial components of the electroretinogram. Normoxic and hypoxemic recordings were taken from nine normal and six streptozotocin-diabetic, anesthetized, paralyzed, and ventilated pigmented rats. Results. When inspired O 2 was reduced the retinal pigment epithelial c-wave component of most of the normal rats diminished, whereas those of the diabetic rats, though initially smaller, were more resistant to the episode of hypoxemia (P = 0.0061). A similar trend was seen in other components. Conclusion. It is proposed that the reduced sensitivity of the diabetic electroretinogram to hypoxemia results from a reduced dependency of the diabetic retina on oxygen. This reduced dependence may follow from a shift in adenosine triphosphate production whereby oxidative phosphorylation is reduced by the high level of retinal intracellular glucose (Crabtree effect). A reduced oxygen demand would cause a transient increase in retinal PO 2 , leading to a reduction in retinal blood flow. The resulting chronic hypoperfusion of the retinal circulation may deprive the retina of vital, non-energy-related substances. Invest Ophthalmol Vis Sci. 1993;34:3246-3252