Effect of Hypoxemia and Hyperglycemia on pH in the Intact Cat Retina

Abstract

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 ϩ ) concentration were obtained from the cat retina, in vivo, using pH-sensitive microelectrodes during normoxia (arterial partial pressure of oxygen [PaO 2 ]=114.5±7.9 mm Hg), normoglycemia (plasma glucose concentration, 117 ± 19 mg/dL), acute hypoxemia (PaO 2 = 29.5 ± 2.2 mm Hg), and acute hyperglycemia (plasma glucose concentration, 303 ± 67 mg/dL). An H ϩ diffusion model was fitted to the outer retinal data to quantify photoreceptor H ϩ 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 ϩ production. Hyperglycemia induced an acute panretinal acidification of 0.12 pH units; however, photoreceptor H ϩ production levels remained unchanged. Retinal pH changes followed the course of arterial PaO 2 and blood glucose changes. Conclusions:The increase in photoreceptor H ϩ production during hypoxemia confirms the importance of glycolysis in the retina. Hyperglycemia-induced pH changes resulted from either increased inner retinal H ϩ production or decreased H ϩ clearance/neutralization. Clinical Relevance:The hyperglcemia-induced acidification that originates in the inner retina suggests that retinal acidosis may contribute to the development of diabetic retinal disease.

Hyperglycemia in extremely low birth weight infants in a predominantly Hispanic population and related morbidities

“…20 Animal and human studies support the relationship between hyperglycemia and circulatory retinal changes, which, in conjunction with hypoxemia, can accelerate the onset and progression of diabetic retinopathy. [21][22][23][24] Furthermore, it is well established that the prevention of proliferative retinopathy in diabetic adults requires the tightest possible glucose control. 22,25 A number of study limitations need to be addressed.…”

Intraretinal pH in Diabetic Cats

“…First, pH measurements on healthy cats showed that the retina acidified by more than 0.1 pH units during acute hyperglycemia (blood glucose >200 mg/dl). 12 Second, during hypoxemia the retina acidified, presumably from a compensatory increase in outer retinal glycolysis. 12 Inner retinal tissue hypoxia occurred in long-term diabetic cats, even in areas where capillary drop-out was not visible.…”

“…12 Second, during hypoxemia the retina acidified, presumably from a compensatory increase in outer retinal glycolysis. 12 Inner retinal tissue hypoxia occurred in long-term diabetic cats, even in areas where capillary drop-out was not visible. 1 It seemed possible that the chronic hyperglycemia and hypoxia caused by diabetes might lead to acidification of the retina and to alterations in glycolytic metabolism as well as other processes.…”

Improved Metabolic Control Results in Better Myogenic Response of Retinal Arterioles in Patients with Diabetes Mellitus Type 1

“…The function of retinal pericytes is known to be altered by elevated blood glucose, which might play a key role in regulation of vessel tone [14, 15]. The exact biochemical mechanism of how vascular endothelial cell function and the contractility of pericytes are modified needs to be defined, and this is subject of intensive research [16,17,18,19,20,21]. On the other hand, there is evidence that insulin itself and glycemic control might alter microcirculation during the therapy of hyperglycemia [13, 22, 23], and therefore it is important to note that the daily insulin dose of the 17 subjects reported here was increased during the study.…”