- The lens is unique in that it has a very low water content (65%) and an extraordinarily high protein content (33%) — essential for the optimal optical function of the lens.
- The remaining solids, including lipids, inorganic ions, organic phosphate, nucleic acids, and various metabolites, comprise only about 2% of the total lens solids.
PROTEINS –
Lens Crystallins — a, ß, and g crystalline. Mainly in cortex of lens.
Noncrystallin Proteins –
Membrane proteins; maybe either intrinsic or extrinsic.
ENZYMES. Many enzymes are associated with the cell membrane, including the transport enzymes (ATPase), alkaline phosphatase, and adenyl cyclase
ELECTROLYTESRelative to the surrounding environment of aqueous humor and vitreous, the lens has a high potassium content and a low sodium content.
Potassium is located principally within the lens cells, while a significant portion of sodium and chloride is found extracellularly.
LENS pH: 6.89,
AMINO ACIDS
The concentration of free amino acids in the mammalian lens is higher than that in the aqueous humor, vitreous, or plasma
CARBOHYDRATES
Energy production in the lens is almost entirely dependent on glucose metabolism.
LIPIDS
The major phospholipid associated with human lens cell membranes is sphingomyelin.
METABOLISM OF LENS
Site – Main location of lens metabolism is in the lens epithelium
Importance of lens metabolism
- The metabolism of lens is entirely directed towards maintenance of transparency.
- Regulation of lens electrolyte balance serves to maintain the normal hydration of the lens, another critical feature in lens transparency.
- Protection of the lens by oxidative damage – the glutathione pathway helps to preserve the oxidative status of the lens.
CARBOHYDRATE METABOLISM
In the lens energy (ATP) production is entirely dependant on metabolism of glucose.
Pathways of Carbohydrate metabolism
- Anaerobic glycolysis provides 70% energy of lens.
- Kreb’s cycle: aerobic metabolism of glucose
- Sorbitol pathway
- HMP shunt
1. ANAEROBIC GLYCOLYSIS
- Energy provided: 2 moles of ATP for each mole of glucose.
- Rate limiting enzyme The first enzyme of the glycolytic pathway, hexokinase, which catalyzes the conversion of glucose to glucose-6-phosphate, is present at very low levels – rate limiting enzyme.
Importance of anaerobic glycolysis:
Anaerobic glycolysis, avoids the problem of oxygen starvation. This is significant in the lens since it is devoid of blood supply and srvies its oxygen from aqueous humor which has a low oxygen tension.
Fate of glucose in anaerobic glycolysis
- About 80% of the glucose entering the lens is converted to lactic acid by means of anaerobic glycolysis.
- Some of this lactic acid is metabolized further by the Krebs cycle, but the majority simply diffuses out into the aqueous humor to be eliminated from the eye.
- This explains why the aqueous leaving the eye has a much higher lactate concentration than newly formed aqueous humor.
2. KREB’S CYCLE (AEROBIC GLUCOSE METABOLISM)
- Site of Krebs’ cycle: This is limited to the lens epithelium where enzymes for Krebs’s cycle are present and adequate oxygen supply from aqueous is present.
- Energy provided: 38 moles of ATP from each mole of glucose. Hence more efficient than glycolysis
- Fate of glucose in Krebs cycle:
Only about 3% of the total glucose is metabolized by means of the Krebs cycle, but because of the efficiency of the pathway this can generate up to 20% of the total ATP in the lens.
Carbon dioxide produced by the Krebs cycle diffuses out of the lens into the aqueous humor.
3. SORBITOL PATHWAY
- The sorbitol pathway of the lens converts glucose to sorbitol and then to fructose using the enzymes aldose reductase and polyol dehydrogenase, respectively.
- Under normal conditions, no more than about 5% of the glucose used by the lens is metabolized by the sorbitol pathway.
Importance of sorbitol pathway: pathogenesis of diabetic cataract.
There is a limited amount of glycolytic pathway enzyme hexokinase in the lens.
When glucose levels in aqueous are elevated (as in DM)
Glucose enters the lens and enters the sorbitol pathway
In the lens, glucose is converted to sorbitol by aldose reductas enzyme
Cell membranes are impermeable to sorbitol and it accumulates within the cells.
Osmotic diffusion of water into the lens occurs
Loss of lens transparency (cataract)
Recent advance: inhibitors of aldose reducatse are being studied to prevent diabetic cataract.
4. HMP PATHWAY
This does not generate a large quantity of ATP.
Importance of HMP pathway
- It generates NADPH:
NADPH is used as a cofactor in sorbitol pathway.
NADPH s required for the maintenance of reduced glutathione by glutathione reductase.
2. It generates pentoses
Pentoses are used in nucleic acid synthesis.
Some pentoses are recycled to enter the glycolytic pathway.
PROTEIN METABOLISM
- Lens protein synthesis takes place mainly in the epithelium and superficial cortex.
- Specific crystallins are synthesized at different times during the development of the lens.
- The protein a-crystallin appears in all lens cells while ß- and g-crystallins are only synthesized by lens fibers.
Importance of lens protein metabolism
There have been a number of studies suggesting that during the aging process lens proteins may be susceptible to changes through oxidative mechanisms and other biochemical reactions such as nonenzymatic glycation
GLUTATHIONE METABOLISM
There is a large amount of glutathione in the lens, particularly in the epithelium and superficial cortex.
Most of the glutathione in the lens is present in a reduced state.
Importance of glutathione
- One of the principal duties of glutathione is to maintain lens protein sulfhydryl groups (-SH) in the reduced state.
- Oxidation of lens protein sulfhydryl groups might lead to cross linkage of proteins, resulting in aggregation and loss of lens transparency.
- The recycling of oxidized glutathione back to the reduced form requires NADPH to NADP which is provided by the HMP pathway.
