"CORNEAL METABOLISM- ENERGY TOCORNEACORNEAL METABOLISM-ENERGY TO CORNEAEpitheliumCornea is exposed to the different external environment so the metabolism is carried outunder a broad range of temperatures. The average temperature of the human cornea has beenestimated to be 34.8°C but this will differ with the extremes of the environmentaltemperature.The corneal epithelium primarily uses glucose and glycogen for energy production. Glucoseenters the cell from the aqueous humour by diffusion, and the corneal epithelial cells storehigh levels of glycogen. Under stress full conditions like hard contact lens wear or traumaepithelial glycogen is rapidly depleted.Glucose Metabolism in Corneal Epitheliumpercentageglycolysis HMP sorbitol The HMP shunt converts hexoses to pentoses required for nucleic acid synthesis andproduces the reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH), ahigh-energy reducing agent required for fatty-acid synthesis and membrane repair. NADPHand pentoses are both required for a tissue with a high mitotic index, like the cornealepithelium. Glucose in the cornea may also enter the sorbitol pathway, which producessorbitol and fructose. In the presence of excess glucose, sorbitol may accumulate in thecornea as it does in the lens and peripheral nerves, causing osmotic cell damage. However,the role of sorbitol in corneal epithelial damage in diabetes is not clear.The corneal epithelium receives its oxygen from the atmosphere under open-eye conditionswhere it is exposed to a partial oxygen pressure of 155 mm Hg in the tears. O2 pressure 200 Series 1 100 0 open eye eyelids closed conditions When the eyelids are closed, the oxygen pressure drops to 55 mm Hg, which is apparentlyadequate to maintain the epithelium, although a degree of epithelial edema does occur duringsleep. (1) Corneal thickness is increased in the morning following overnight eyelid2 closure.The cornea consumes approximately 3.5 µL of oxygen/cm /hour. (2, 3) Under aerobic conditions, pyruvate from glycolysis can enter thetricarboxylic acid cycle, although the activity of the pathway is low in the epithelium becauseof the paucity of mitochondria (2, 4). Under hypoxic conditions (e.g., during contact lenswear), pyruvate is converted to lactate which maintain intracellular pH at between 7.3 to 7.4.Lactate cannot diffuse across the apical barrier and builds up in the stroma (5). Associatedwith this lactic acid is anoxia of the epithelial cells, leading to epithelial edema that clinicallycan cause halo formation, glare, and reduced contrast sensitivity. The acidification of theextracellular fluid may interfere with cellular metabolism and mitosis, leading to epithelialthinning and erosion (6-7). The cytochrome P450 system is also functional in the corneal epithelium. Under conditionsof hypoxia or inflammation, arachidonic acid is metabolized through this pathway with theproduction of two eicosanoids, 12(R)-hydroxyeicosa-tetraenoic acid (12(R)HETE) and12(R)-hydroxyei-cosatrienoic acid (12(R)HETrE) (8-9). Both of these eicosanoids havepathophysiological importance. 12(R) HETE has the potential to diffuse from the epithelium+ + to the endothelium and inhibit Na /K ATPase and the endothelial metabolic pump,ultimately causing corneal swelling. 12(R) HETrE can serve as a chemoattractant and induceStromal neovascularisation. Contact lenses that do not fit well or have low oxygen permeability can lead to inflammation and hypoxia from 12(R) HETE or lactate, which canhave an adverse effect on the structure and function of the corneal endothelium. (10) ENDOTHELIUMThe endothelium utilizes the same carbohydrate metabolism pathways as the epithelium. Thetransport function of the cells in the endothelial monolayer requires oxidative activity that isfive to six times that of the cells in the epithelium (11). Atmospheric oxygen is the primarysource of oxygen to the endothelium. Interruption of this oxygen supply by low-oxygen transmissibility contact lenses or a low- oxygen environment will result in a ? Shift to anaerobic metabolism,? A concurrent increase in Stromal lactic acid and CO ,2 ? And a drop in Stromal pH.Glycolysis accounts for 93% of the conversion of glucose-6-phosphate to pyruvate in theendothelium. The aerobic tricarboxylic acid cycle converts 30% of the pyruvate to ATP,whereas the remaining 70% is converted to lactic acid by the anaerobic pathway of lactatedehydrogenase.In addition, this hypoxia can stimulate epithelial production of 12(R) HETE,+ + a potent inhibitor of the endothelial Na /K ATPase (9, 12). Acute reversible clinical changesseen with hypoxia include stromal swelling, endothelial dysfunction, and endothelialblebbing. Chronic hypoxia can lead to irreversible endothelial polymegathism andpleomorphism. Pulse et al; have shown chronic hypoxia in humans alters the endothelium'sability to reverse induced swelling (13).The endothelium also has the ability to extract and metabolize dehydro-L-ascorbic acid fromthe aqueous humor. Bode et al found that bovine endothelial cells can take up dehydro-L- ascorbic acid, the oxidized form of ascorbic acid, and reduce it to ascorbic acid(14). Ascorbic acid is a free-radical scavenger that may act to protect the cells from radiation- induced free-radical damage. "