Search PubMed⌕ Search

Biomedical subjects

Robert A Linsenmeier

Publications and source records attributed to Robert A Linsenmeier.

9 recordsLinked to original sources
PubMed2006

The electroretinogram components in Abyssinian cats with hereditary retinal degeneration.

PURPOSE: To examine phototransduction using the a-wave and other aspects of retinal function with the intraretinal b- and c-waves at different stages of an inherited photoreceptor degeneration in Abyssinian cats. METHODS: Vitreal and intraretinal ERGs were recorded from eight dark-adapted, anesthetized Abyssinian cats. Brief bright flashes were used to elicit vitreal a- and b-waves. Longer, weaker flashes were used to elicit intraretinal b- and c-waves. Stages 1 through 4 of the disease were characterized ophthalmoscopically. Parameters of the Lamb and Pugh a-wave model (a(max), A, and t(eff)) for the Abyssinian cats were compared with those for normal cats. Light microscopy was used to count photoreceptor nuclei. RESULTS: The maximum a-wave amplitude, a(max), was significantly smaller in stage 1, and continued to decrease (stage 1: 50% of normal, stage 2: 28%, stage 3: 27%; and stage 4: unrecordable). There was a small, but not significant, decrease in the amplification constant A from 0.24 +/- 0.11 s(-2) in normal cats to 0.16 +/- 0.08 s(-2) in Abyssinian cats. The intraretinal b- and c-wave amplitudes decreased most dramatically during the early stage of the disease. Affected animals had fewer photoreceptors than unaffected Abyssinians or control animals. The number of photoreceptors declined most rapidly in the inferior periphery. CONCLUSIONS: The amplitudes of all ERG components were already reduced significantly by stage 1 and progressively declined. The lack of major changes in a-wave model parameters indicates that the degeneration is probably not due to a mutation in transduction proteins. Losses of photoreceptor function were larger than losses of photoreceptor nuclei.

Animals↗
PubMed2006

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 approximately 50% 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.

Animals↗
PubMed2005

Effect of hypoxemia and hyperglycemia on pH in the intact cat retina.

OBJECTIVE: To examine the effects of acute hypoxemia and hyperglycemia on retinal pH to understand hyperglycemia-induced changes in the normal intact cat retina. METHODS: Spatial profiles of extracellular hydrogen ion (H+) concentration were obtained from the cat retina, in vivo, using pH-sensitive microelectrodes during normoxia (arterial partial pressure of oxygen [PaO2] = 114.5 +/- 7.9 mm Hg), normoglycemia (plasma glucose concentration, 117 +/- 19 mg/dL), acute hypoxemia (PaO2 = 29.5 +/- 2.2 mm Hg), and acute hyperglycemia (plasma glucose concentration, 303 +/- 67 mg/dL). An H+ diffusion model was fitted to the outer retinal data to quantify photoreceptor H+ production. The inner retinal pH was also examined. RESULTS: Hypoxemia induced a mean acute panretinal acidification of 0.16 pH units that originated from a 2.55-fold increase in net photoreceptor H+ production. Hyperglycemia induced an acute panretinal acidification of 0.12 pH units; however, photoreceptor H+ production levels remained unchanged. Retinal pH changes followed the course of arterial PaO2 and blood glucose changes. CONCLUSIONS: The increase in photoreceptor H+ production during hypoxemia confirms the importance of glycolysis in the retina. Hyperglycemia-induced pH changes resulted from either increased inner retinal H+ production or decreased H+ clearance/neutralization. Clinical Relevance The hyperglycemia-induced acidification that originates in the inner retina suggests that retinal acidosis may contribute to the development of diabetic retinal disease.

Acidosis↗
PubMed2005

Retinal arterial occlusion leads to acidosis in the cat.

This study investigated the changes in pH during retinal artery occlusion by means of extracellular H+ concentration ([H+]o) measurements in the retina under both air and 100% O2 ventilation. Occlusion was produced in intact anesthetised cats by pressing with a probe onto a retinal artery. [H+]o profiles were recorded across the retina with pH sensitive microelectrodes. The average inner retinal [H+]o increased during occlusion, resulting in an acidification of as much as 0.10 pH units, even under 100% O2 ventilation. The inner retinal H+ profile magnitude decreased during occlusion due to impaired clearance. The average outer retinal H+ profile magnitude also increased even though outer retinal H+ production did not increase during occlusion. This might be due to H+ diffusion from the inner retina to the outer retina, which is opposite to the flux in the normal retina. After reperfusion, [H+]o returned to its preocclusion value. In conclusion, arterial occlusion leads to acidification of the retina. Enhanced oxygenation during occlusion did not decrease this acidification. This may explain why increasing PO2 in the retina by enhanced O2 breathing improves retinal function during and after occlusion, but does not totally reverse the effect of occlusion.

Acidosis↗
PubMed2004

Hyperoxia promotes electroretinogram recovery after retinal artery occlusion in cats.

PURPOSE: This work assessed the hypotheses that (1) hyperoxia is preferable to air breathing during retinal arterial occlusion, (2) hyperoxia during occlusion is beneficial in promoting recovery from arterial occlusion, and (3) hyperoxia has value even if it is delayed relative to the onset of the occlusion. METHODS: Reversible branch retinal artery occlusion was produced by pressing with a glass probe onto an artery emerging from the superior part of the optic disc in the retina of anesthetized cats. During 2-hour occlusion episodes, the cats breathed 100% O(2), 1 hour of air and 1 hour of 100% O(2), 1 hour of air and 1 hour of 70% O(2), or air. Intraretinal ERGs were recorded before, during, and after the occlusion. RESULTS: Hyperoxia during occlusion preserved intraretinal b-wave amplitude at 86% +/- 12% of normal; longer durations of increased oxygenation maintained the b-wave at higher levels during occlusion and increased the probability of b-wave recovery after occlusion; higher O(2) content in the breathing gas increased b-wave amplitude during recovery; and hyperoxia during occlusion decreased the time it took for the b-wave to recover after the occlusion. CONCLUSIONS: Hyperoxia is preferable to air breathing during retinal arterial occlusion not only for maintaining b-wave amplitude during occlusion, but also for providing a shorter recovery time and better percentage recovery after the end of the occlusion. Even if it is not possible to begin hyperoxia at the onset of occlusion, it may still be valuable.

Animals↗
PubMed2003

Retinal oxygen: fundamental and clinical aspects.

We reviewed research on retinal oxygen (O2) distribution and use, focusing on O2 microelectrode studies in animals with circulatory patterns similar to those of humans. The inner and outer halves of the retina are different domains in terms of O2. Understanding their properties can suggest mechanisms of and therapies for retinal diseases. Inner retinal PO2 averages about 20 mm Hg. Effective O2 autoregulation of the retinal circulation ensures that inner retinal PO2 is relatively uninfluenced by systemic hypoxia and hyperoxia and increased intraocular pressure in healthy animals. Failures of the retinal circulation lead to tissue hypoxia that underlies the vasoproliferation in diabetic retinopathy and retinopathy of prematurity. Choroidal blood flow is not regulated metabolically, so systemic hypoxia and elevated intraocular pressure lead to decreases in choroidal PO2 and photoreceptor O2 consumption. The same lack of regulation allows choroidal PO2 to increase dramatically during hyperoxia, offering the potential for O2 to be used therapeutically in retinal vascular occlusive diseases and retinal detachment.

Animals↗
PubMed2003

Effect of acute hyperglycemia on oxygen and oxidative metabolism in the intact cat retina.

PURPOSE: The Crabtree effect is the phenomenon of inhibition of respiration by glycolysis, as a result of elevated glucose levels. It is not certain whether the Crabtree effect occurs in the retina, which has a high glycolytic capacity. In the current study, in vivo photoreceptor oxygen consumption was examined during the normo- and hyperglycemic states in the dark-adapted cat retina to determine whether the Crabtree effect occurs in the outer retina. METHODS: Spatial profiles of oxygen tension were obtained in the cat retina, in vivo, with the use of oxygen microelectrodes during control conditions and acute (5.19 +/- 0.83 hour) episodes of hyperglycemia (blood glucose, >350 mg/dL). The outer retinal portions of the profiles were fitted to a model of oxygen diffusion to quantify photoreceptor oxygen consumption. RESULTS: Photoreceptor oxygen consumption did not significantly change during hyperglycemia compared with control conditions. Choroidal PO(2) decreased during hyperglycemia by an average of 5.8 +/- 7.4 mm Hg. This led to an increase in the fraction of O(2) used by the photoreceptors that was derived from the inner retina. Choroidal PO(2) did not recover when blood glucose levels were returned to normal. Average inner retinal PO(2) was not affected by the episodes of hyperglycemia. CONCLUSIONS: The Crabtree effect does not occur to any significant degree in the outer retina, because hyperglycemia did not affect photoreceptor oxygen consumption. Choroidal PO(2) decreased during hyperglycemia, and the oxygen deficit was made up by the retinal circulation.

Acute Disease↗
PubMedDate not supplied

Quantification of in vivo anaerobic metabolism in the normal cat retina through intraretinal pH measurements.

We examined intraretinal [H+] in the intact retina of anesthetized cats using H+-sensitive microelectrodes to obtain spatial profiles of extracellular [H+]. One H+ is produced when an anaerobically generated ATP is utilized. We theorized that H+ production directly reflects anaerobic glucose consumption. From the choroid (pH approximately 7.40), [H+]o steadily increased to a maximum concentration in the proximal portion of the outer nuclear layer (pH approximately 7.20). The shape of the profile was always concave down, indicating that a net production of H+ occurred across the avascular outer retina. A three-layer diffusion model of the outer retina was developed and fitted to the data to quantify photoreceptor H+ extrusion into the extracellular space (Q(OR-H+)). It was determined that the outer segment (OS) layer had negligible H+ extrusion. The data were then refitted to a special three-layer model in which the OS layer Q(H+) was set equal to zero, but in which the inner segments and outer nuclear layer produced H+. The resulting Q(OR-H+) was several orders of magnitude lower than previous measurements of Q(OR-lactate), which were based on choroidal mass balances of lactate. Stoichiometrically, one H+ is produced for each lactate produced, so we concluded that Q(OR-H+) is a measure of net rather than total H+ production. Because retinal acid production is so high, the retina must contain efficient H+ clearance and/or neutralization mechanisms that prevent severe acidosis. The effect of light on retinal extracellular [H+] and Q(OR-H+) was also examined. As expected, light adaptation caused a retinal alkalinization that resulted from a 52% reduction in Q(OR-H+). This is in agreement with previous studies that have shown that both oxidative (e.g. Haugh et al., 1990) and glycolytic metabolism (Wang et al., 1997a,c) in the photoreceptor are decreased by a factor of 2 during light adaptation. Although we could not obtain absolute values for outer retinal glycolysis, changes in Q(OR-H+) appear to directly reflect changes in glycolytic metabolism.

Adaptation, Ocular↗