Stromal lactate accumulation can account for corneal oedema osmotically following epithelial hypoxia in the rabbit.

Abstract

SUMMARY1. The mechanism underlying stromal oedema subsequent to epithelial hypoxia was investigated in isolated rabbit corneas.2. Stromas swelled about 20 ,tm following a 1 hr period of tear side hypoxia in both whole corneal isolates and in preparations in which fluid movement across the endothelium was blocked with silicone oil. In the experiments using whole corneas, stromal thickness was independent of tear side oxygen tension as long as aqueous humour Po2 was greater than 40 mmHg.3. Neither epithelial thickness nor epithelial electrical resistance, a measure of total ion permeability, was significantly affected by blocking respiration. 4. A 10 'C reduction in corneal temperature markedly reduced the rate of hypoxic swelling, suggesting the involvement of a metabolism-dependent hydrating process and implicating the stromal accumulation of a catabolyte.5. When CN-was used to mimic the hypoxic effect in isolated whole corneas, the passive 36C1 unidirectional flux was unaffected, but lactate production rate and stromal [lactate] more than doubled.6. These measurements were used with a mathematical model for corneal hydration dynamics to examine the causes of hypoxic oedema. The principal conclusions were: epithelial hypoxia enhances epithelial lactate production and release to the stroma; this process causes an increase in stromal lactate concentration and a decrease in stromal NaCl concentration (primarily through dilution); stromal lactate accumulation exceeds in osmotic load the dilutional effect on [NaCl], producing stromal oedema. Whereas hypoxia produces corneal metabolic acidosis, effects on endothelial permeability of HC03-transport need not be postulated to explain the stromal oedema that results from hypoxia.

CD147 Required for Corneal Endothelial Lactate Transport

“…Efflux is driven by the 2-fold [lactate] gradient from cornea to anterior chamber. 5,6 Facilitated transport of lactate has been extensively studied in rabbit corneal endothelium.…”

“…The accumulation of lactate within the cornea can create an osmotic load that will increase stromal hydration and corneal thickness. 5 To maintain corneal hydration and transparency, the large quantity of lactate must be simultaneously exported out. Since the surface corneal epithelial cells are impermeable to lactate, lactate efflux must take place across the endothelium.…”

“…Efflux is driven by the 2-fold [lactate] gradient from cornea to anterior chamber. 5,6 Facilitated transport of lactate has been extensively studied in rabbit corneal endothelium.7,8 Lactate along with a H þ is cotransported through the plasma membrane of many cell types via stereospecific, pH-dependent monocarboxylate transporters (MCT1-4).9-18 Recently, we have identified MCT1, -2, and -4 in human, 19 bovine, 20 and rabbit 21 corneal endothelium. Interference with primary or secondary active transporters that regulate intracellular pH (pH i ), reduced buffering by removal of HCO 3 À , or inhibition of carbonic anhydrases slowed lactate fluxes, led to corneal lactate accumulation, and increased corneal thickness, indicating that lactate efflux is a significant component of the endothelial pump.…”

“…Efflux is driven by the 2-fold [lactate] gradient from cornea to anterior chamber. 5,6 Facilitated transport of lactate has been extensively studied in rabbit corneal endothelium. 7,8 Lactate along with a H þ is cotransported through the plasma membrane of many cell types via stereospecific, pH-dependent monocarboxylate transporters (MCT1-4).…”

Variaciones diurnas de espesor y curvatura corneal central y paracentral

“…La disminución de aporte de oxígeno que tiene lugar en el cierre ocular nocturno lleva a un metabolismo anaeróbico que produce un aumento de ácido láctico. Como consecuencia se produce un aumento de la presión osmótica que favorece la difusión de agua desde el humor acuoso hacia el estroma, con el consecuente aumento de espesor corneal (24). Cuando se compara el espesor corneal obtenido durante un periodo de 10 horas, observamos una variación estadísticamente significativa en todas las localizaciones estudiadas.…”